The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular rec...The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.展开更多
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
Objective:To investigate the delivery modes of women with repeat pregnancies involving uterine scars and their effects on both mothers and neonates.Methods:A study was conducted on 100 patients treated at Shenzhen Mat...Objective:To investigate the delivery modes of women with repeat pregnancies involving uterine scars and their effects on both mothers and neonates.Methods:A study was conducted on 100 patients treated at Shenzhen Maternity and Child Healthcare Hospital from July 2023 to July 2024.The participants were divided into a control group and an observation group,with 50 cases in each.The division was based on the indications for prior cesarean section,cervical maturity,postpartum complications,and thickness of the cesarean scar.The control group underwent cesarean delivery,while the observation group experienced vaginal delivery.The two groups were compared in terms of intrapartum blood loss,postpartum blood loss within 2 hours,length of hospital stay,Apgar scores at 1-minute post-birth,and incidences of neonatal fever and jaundice.Results:The observation group had significantly lower intrapartum blood loss,postpartum blood loss within 2 hours,and shorter hospital stays compared to the control group(P<0.05).Additionally,the Apgar scores at 1 minute post-birth were significantly higher in the observation group(P<0.05).The incidence of neonatal fever and jaundice was significantly lower in the observation group(P<0.05).These differences were statistically significant.Conclusion:Vaginal delivery has high clinical value for women with repeat pregnancies involving uterine scars.It reduces maternal intrapartum and postpartum blood loss,shortens hospital stays,improves neonatal Apgar scores,and decreases the incidences of neonatal fever and jaundice.This method is worthy of clinical application and promotion.展开更多
In recent years,adeno-associated viruses(AAVs)have emerged as leading vectors in gene therapy,with several FDA-approved treatments and ongoing clinical trials demonstrating their effectiveness in treating inherited re...In recent years,adeno-associated viruses(AAVs)have emerged as leading vectors in gene therapy,with several FDA-approved treatments and ongoing clinical trials demonstrating their effectiveness in treating inherited retinal diseases,hemophilia,and Duchenne muscular dystrophy,among others.However,AAV-based therapies still face challenges,including immune responses and side effects,due to high viral doses.To address these challenges,various strategies have been developed,such as creating new viral capsids,optimizing gene expression regulation,and improving delivery methods.Localized delivery is a promising direction,utilizing the tissue tropism of AAVs to reduce systemic side effects and lower the required viral dose,thus improving targeting and efficiency,especially for organs that are difficult to treat with conventional methods.These innovations have opened new pathways for the clinical application of AAVs.This review aims to provide a comprehensive summary of the various applications of AAVs,offer valuable insights for future research directions,and holds significant importance for researchers and clinicians in the field.As AAV therapy continues to evolve,this article emphasizes its transformative potential in treating genetic diseases,indicating the central role of AAV in the future of gene therapy.展开更多
Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or force...Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or forceps to save the newborn. The purpose of this study was to determine the prevalence of vacuum-assisted vaginal delivery (VAVD) and its associated short-term maternal and neonatal outcomes at Ndola Teaching Hospital. Methods: A retrospective cross-sectional descriptive study through the analysis of routine data for women with singleton-term pregnancies who delivered by vacuum compared with spontaneous vaginal delivery was done at a tertiary hospital for the years 2020 and 2021. Chi-square and Logistic regression were used to investigate factors of vacuum delivery and to adjust for potential confounders. Results: Results showed that VAVD was mostly performed in women who had delayed second stage of labour (25.4%), maternal exhaustion (16.0%), foetal distress in the second stage of labour (12.3%). The overall VAVD prevalence was 3.7% (581/15591). Logistic regression showed that multiparous women were noted to be 87.5% (aOR 0.125;95% CI 0.025 - 0.629;p = 0.012) less likely to undergo VAVD compared to nulliparous women. Registrars were almost 6 times (aOR 5.650;95% CI 1.458 - 22.222, p = 0.012) more likely to conduct VAVD compared to midwives. Episiotomy was 3 times (aOR 3.390;95% CI 1.185 - 9.524;p Conclusion: The findings indicate the underutilisation of VAVD at NTH based on the low prevalence of 3.7%. VAVD outcomes were affected by multiparity, skill level and Episiotomy procedure, in addition, VAVD influenced admission to the NICU. Hence, there is a need to increase skills in VAVD among first-line healthcare workers such as midwives and intern doctors.展开更多
Effective therapeutic intervention for central nervous system(CNS)diseases,including brain tumors and neurodegenerative disorders,is significantly challenged by the formidable blood-brain barrier(BBB).This biological ...Effective therapeutic intervention for central nervous system(CNS)diseases,including brain tumors and neurodegenerative disorders,is significantly challenged by the formidable blood-brain barrier(BBB).This biological barrier severely restricts the passage of most drug candidates,resulting in inefficient delivery to pathological sites and substantially contributing to high clinical trial failure rates for CNS therapies.Engineered nanoparticles have emerged as promising functional material systems capable of navigating these delivery obstacles,offering advantages like encapsulating diverse agents,controlled release,and targeted delivery.This review comprehensively analyzes innovative nanoparticle strategies specifically designed to overcome the BBB and achieve precise CNS delivery via systemic administration.We highlight the critical multi-step biological cascade required for successful therapeutic outcomes:maintaining colloidal stability in circulation,efficiently penetrating the BBB,achieving specific accumulation at the disease site,and effectively engaging target cells.Despite significant advancements,clinical translation of these nanoparticle systems remains limited.A thorough understanding of this multi-step process is paramount to accelerating the clinical application of brain-targeted nanomedicines.展开更多
With the rapid development of low-altitude economy and unmanned aerial vehicles (UAVs) deployment technology, aerial-ground collaborative delivery (AGCD) is emerging as a novel mode of last-mile delivery, where the ve...With the rapid development of low-altitude economy and unmanned aerial vehicles (UAVs) deployment technology, aerial-ground collaborative delivery (AGCD) is emerging as a novel mode of last-mile delivery, where the vehicle and its onboard UAVs are utilized efficiently. Vehicles not only provide delivery services to customers but also function as mobile ware-houses and launch/recovery platforms for UAVs. This paper addresses the vehicle routing problem with UAVs considering time window and UAV multi-delivery (VRPU-TW&MD). A mixed integer linear programming (MILP) model is developed to mini-mize delivery costs while incorporating constraints related to UAV energy consumption. Subsequently, a micro-evolution aug-mented large neighborhood search (MEALNS) algorithm incor-porating adaptive large neighborhood search (ALNS) and micro-evolution mechanism is proposed. Numerical experiments demonstrate the effectiveness of both the model and algorithm in solving the VRPU-TW&MD. The impact of key parameters on delivery performance is explored by sensitivity analysis.展开更多
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)re...Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.展开更多
The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers...The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed.Beyond these vectors,polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities,such as improving the stability,cellar uptake and endosomal escape of nucleic acid drugs,along with precise delivery to targeted tissues.This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery,focusing on key cationic polymers,nanocarrier types,and preparation methods.It also highlights targeted diseases,strategies to improve delivery efficiency,and potential future directions in this research area.The review is hoped to inspire the development,optimization,and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.展开更多
Unmanned aerial vehicles(UAVs)are widely used in situations with uncertain and risky areas lacking network coverage.In natural disasters,timely delivery of first aid supplies is crucial.Current UAVs face risks such as...Unmanned aerial vehicles(UAVs)are widely used in situations with uncertain and risky areas lacking network coverage.In natural disasters,timely delivery of first aid supplies is crucial.Current UAVs face risks such as crashing into birds or unexpected structures.Airdrop systems with parachutes risk dispersing payloads away from target locations.The objective here is to use multiple UAVs to distribute payloads cooperatively to assigned locations.The civil defense department must balance coverage,accurate landing,and flight safety while considering battery power and capability.Deep Q-network(DQN)models are commonly used in multi-UAV path planning to effectively represent the surroundings and action spaces.Earlier strategies focused on advanced DQNs for UAV path planning in different configurations,but rarely addressed non-cooperative scenarios and disaster environments.This paper introduces a new DQN framework to tackle challenges in disaster environments.It considers unforeseen structures and birds that could cause UAV crashes and assumes urgent landing zones and winch-based airdrop systems for precise delivery and return.A new DQN model is developed,which incorporates the battery life,safe flying distance between UAVs,and remaining delivery points to encode surrounding hazards into the state space and Q-networks.Additionally,a unique reward system is created to improve UAV action sequences for better delivery coverage and safe landings.The experimental results demonstrate that multi-UAV first aid delivery in disaster environments can achieve advanced performance.展开更多
Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,lim...Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,limitations in space and energy supply have resulted in the inability to perform multiple diagnostic and treatment tasks using a single capsule.In this study,we developed a dual-functional capsule robot(DFCR)for drug delivery and tissue biopsy based on magnetic torsion spring technology.The delivery module was shown to rotate the push rod with a thrust of 894 mN to release approximately 0.3 mL of semisolid drug.The biopsy module used a built-in blade to cut tissue with a shear stress of 22.87 MPa,producing a sample of approximately 1.8 mm3.Additionally,a five-degree-of-freedom permanent magnet drive system was developed.By adjusting the strength of the unidirectional magnetic field generated by an external magnet,the capsule can be wirelessly controlled to sequentially trigger the two functions.Ex vivo tests on porcine stomachs confirmed the feasibility of the prototype capsule(12 mm in diameter and 45 mm in length)in active movement,medication,and tissue biopsy.The newly developed DFCR further expands the clinical application prospects of WCE robots in minimally invasive surgery.展开更多
Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive mol...Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.展开更多
Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are des...Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.展开更多
Four glycoluril-based amphiphilic molecular clips(AMCs)M1~M4 have been prepared for intracellular delivery of short DNA.M1~M4 have two methyl groups on its convex surface and four cations on its aromatic side arm,whic...Four glycoluril-based amphiphilic molecular clips(AMCs)M1~M4 have been prepared for intracellular delivery of short DNA.M1~M4 have two methyl groups on its convex surface and four cations on its aromatic side arm,which can be used to construct self-assembled nanoparticles in aqueous solution driven by hydrophobic interaction.Dynamic light scattering experiments show that M1 and M2 can be driven hydrophobically to aggregate into extremely stable nanoparticles in water at the micromolar concentrations.Fluorescence titration and zeta potential experiments support that the nanoparticles formed by M1 and M2 are able to efficiently encapsulate short DNA(sDNA).Fluorescence imaging and flow cytometry studies reveal that their nano sizes enable intracellular delivery of the encapsulated sDNA into both normal and cancer cells,with delivery percentage reaching up to 94%,while in vitro experiments indicate that the two compounds have excellent biocompatibility and low cytotoxicity.展开更多
Spores and pollen,as ubiquitous organisms found in nature,possess a remarkable core-shell structure and intricate surface morphology.These tiny particles are notable for their dimensional uniformity,sustainable utiliz...Spores and pollen,as ubiquitous organisms found in nature,possess a remarkable core-shell structure and intricate surface morphology.These tiny particles are notable for their dimensional uniformity,sustainable utilization,environmental friendliness,porosity,amphiphilicity,and strong adhesive properties.In addition,they display excellent biocompatibility and biodegradability,which significantly enhances the stability and targeting of drugs within the body.Spores and pollen can be extracted using methods such as acidic solutions,alkaline solutions,or enzyme treatments to obtain sporopollenin,which is an extremely resilient and chemically inert complex biopolymer.The sporopollenin extracted through this process removes the original bioactive substances,such as cell nuclei,enzymes,and DNA,providing greater drug loading capacity and containing no potential allergens or immunogens,thus further enhancing its drug loading capacity and improving safety in therapeutic applications.Due to these beneficial attributes,spores,pollen and sporopollenin have gained widespread use in a variety of drug delivery systems,such as targeted delivery,sustained drug delivery,toxicity mitigation,flavor masking,vaccine delivery,delivery of labile substances,and other applications.This review introduces the types of natural spores and pollen commonly used in drug delivery systems,including their main components,common effects,and uses in drug delivery systems,and so on.It subsequently summarizes novel optimization methods in their processing,such as physical treatment,surface modification,and chemical modification,which enable higher drug loading efficiency,stability,and targeting,among other benefits.Additionally,this paper reviews the research progress and applications of natural spores,pollen,and sporopollenin in drug delivery systems,while also touching on some innovative research content,such as novel nanomotor microcarriers developed based on pollen.Based on these research findings,we further elaborate on the advantages of spores,pollen,and sporopollenin in drug delivery systems.For example,they have high stability and drug loading capacity,good adhesion,excellent targeting,and are easy to modify functionally.Currently,they show promising prospects in the fields of targeted drug delivery,sustained-release drug delivery,as well as the delivery of drugs that are effective but slightly toxic,and are often used in research on the treatment of diseases such as cancer and inflammation.We have also highlighted the challenges they face in various applications and identified some issues that need to be addressed,including difficulties in largescale production,the need to improve extraction and purification processes,and the existence of a low but still noteworthy risk of allergies,in order to fully leverage their potential in drug delivery applications.According to current research,although spores,pollen,and sporopollenin face some unresolved issues in clinical drug delivery,they still have great potential overall and are expected to become a new generation of green drug delivery platforms.In the future,further research into their unique physical and chemical properties and structural characteristics will help develop more efficient and stable drug delivery systems to meet diverse treatment needs.We believe that continued exploration of natural spores,pollen,and sporopollenin will drive this emerging field to achieve continuous breakthroughs and progress,ultimately making an important contribution to the cause of human health.展开更多
Microneedle-mediated drug delivery systems(MDDS)have experienced robust growth in recent years,with designers leveraging their creativity to apply these systems for direct drug delivery to the skin,mucous membranes,bl...Microneedle-mediated drug delivery systems(MDDS)have experienced robust growth in recent years,with designers leveraging their creativity to apply these systems for direct drug delivery to the skin,mucous membranes,blood vessel walls and even internal organs.In order to achieve precise drug delivery,various delicately conceived drug release modes based on MDDS have been developed.Herein,to elucidate the design concepts of numerous reported MDDS,we have categorized them into two levels(Level-ⅠMDDS and Level-ⅡMDDS)depending on whether nanoscale and microscale carriers are integrated within the microneedles.In this work,the design strategies of MDDS,as well as the current status of their applications in targeted and intelligent drug delivery were reviewed,while their prospects and challenges for future industrialization and clinical applications were also discussed.展开更多
BACKGROUND The rising global burden of liver diseases,such as non-alcoholic fatty liver disease and liver fibrosis,has necessitated innovative therapeutic approaches.Plant-based therapies,recognized for their anti-inf...BACKGROUND The rising global burden of liver diseases,such as non-alcoholic fatty liver disease and liver fibrosis,has necessitated innovative therapeutic approaches.Plant-based therapies,recognized for their anti-inflammatory and antioxidant properties,have shown promising effects.However,poor bioavailability limits their clinical application.AIM To map global research trends,key contributors,and emerging themes in plant-based therapies combined with advanced drug delivery systems for liver health.METHODS Using the Scopus database,645 documents were retrieved and analyzed using bibliometric tools Biblioshiny and VOSviewer.Analysis focused on publication trends,geographical contributions,and advancements in drug delivery technologies,including nanoparticles,liposomes,and polymeric micelles.Metrics such as publication growth rate,authorship collaboration,and thematic clustering were assessed.RESULTS The dataset spans 43 years(1981-2024),with an annual growth rate of 11.09%in the number of publications.Research output is dominated by China(33%),followed by the United States(24%)and India(18%).Collaborative studies accounted for 24.34%of publications,with an average of 5.81 co-authors per document.Key innovations include nanoparticle encapsulation of curcumin and silymarin,improving bioavailability by up to 85%.Highly cited studies demonstrated the antioxidant,anti-inflammatory,and anti-fibrotic properties of these compounds.For instance,curcumin nanoparticles showed a 70%improvement in solubility,and silymarin liposomal formulations enhanced therapeutic efficiency by 62%.Thematic analysis revealed a transition from basic clinical observations to molecular and pharmacokinetic research,with a focus on oxidative stress mitigation and hepatoprotection.CONCLUSION This study highlights the growing synergy between plant-based therapies and advanced drug delivery systems,with significant contributions from Asian and Western countries.Future efforts should prioritize clinical trials,standardization of plant extract formulations,and interdisciplinary approaches to maximize therapeutic outcomes.The findings provide a foundation for integrating plant-derived compounds into evidence-based hepatological therapies,addressing critical challenges in bioavailability and safety.展开更多
Current treatments for glioblastoma face challenges such as the blood-brain barrier and lack of targeted therapy,compounded by the aggressive nature,high invasiveness,and heterogeneity of the disease.Exosomes,a subtyp...Current treatments for glioblastoma face challenges such as the blood-brain barrier and lack of targeted therapy,compounded by the aggressive nature,high invasiveness,and heterogeneity of the disease.Exosomes,a subtype of extracellular vesicles are emerging as promising nanocarrier drug delivery systems to address these limitations.Exosomes released by all cell types can be easily obtained and modified as delivery vehicles or therapeutic agents.A systematic review was conducted to evaluate various methods for exosome isolation,characterization,engineering or modification,drug loading and delivery efficiency,including exosome biodistribution and treatment efficacy.A search of four databases for in vitro and in vivo studies(2000–,2023)identified 6165 records,of which 23 articles were found eligible and included for analyses.Most studies applied ultracentrifugation(UC)for exosomes isolation.Cancer cell lines being the most frequently used source of exosomes,followed by stem cells.The incubation approach was predominantly utilized to modify exosomes for drug loading.In vivo analysis showed that exosome biodistribution was primarily concentrated in the brain region,peaking in the first 6 h and remained moderately high.Compared to native exosomes and untreated control groups,utilizing modified native exosomes(cargo loaded)for treating glioblastoma disease models led to more pronounced suppression of tumor growth and proliferation,enhanced stimulation of immune response and apoptosis,effective restoration of drug chemosensitivity,increased anti-tumor effect and prolonged survival rates.Modified exosomes whether through incubation,sonication,transfection,freeze-thawing or their combination,improve targeted delivery and therapeutic efficacy against glioblastoma.展开更多
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
基金supported by the National Natural Science Foundation of China,Nos.82301093(to QC)and 22334004(to HY)the Fuzhou University Fund for Testing Precious Equipment,No.2025T038(to QC)。
文摘The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
文摘Objective:To investigate the delivery modes of women with repeat pregnancies involving uterine scars and their effects on both mothers and neonates.Methods:A study was conducted on 100 patients treated at Shenzhen Maternity and Child Healthcare Hospital from July 2023 to July 2024.The participants were divided into a control group and an observation group,with 50 cases in each.The division was based on the indications for prior cesarean section,cervical maturity,postpartum complications,and thickness of the cesarean scar.The control group underwent cesarean delivery,while the observation group experienced vaginal delivery.The two groups were compared in terms of intrapartum blood loss,postpartum blood loss within 2 hours,length of hospital stay,Apgar scores at 1-minute post-birth,and incidences of neonatal fever and jaundice.Results:The observation group had significantly lower intrapartum blood loss,postpartum blood loss within 2 hours,and shorter hospital stays compared to the control group(P<0.05).Additionally,the Apgar scores at 1 minute post-birth were significantly higher in the observation group(P<0.05).The incidence of neonatal fever and jaundice was significantly lower in the observation group(P<0.05).These differences were statistically significant.Conclusion:Vaginal delivery has high clinical value for women with repeat pregnancies involving uterine scars.It reduces maternal intrapartum and postpartum blood loss,shortens hospital stays,improves neonatal Apgar scores,and decreases the incidences of neonatal fever and jaundice.This method is worthy of clinical application and promotion.
基金supported by the Guiding Funds of Central Government for Supporting the Development of the Local Science and Technology(2024BSB012)National Natural Science Foundation of China(No.81772833).
文摘In recent years,adeno-associated viruses(AAVs)have emerged as leading vectors in gene therapy,with several FDA-approved treatments and ongoing clinical trials demonstrating their effectiveness in treating inherited retinal diseases,hemophilia,and Duchenne muscular dystrophy,among others.However,AAV-based therapies still face challenges,including immune responses and side effects,due to high viral doses.To address these challenges,various strategies have been developed,such as creating new viral capsids,optimizing gene expression regulation,and improving delivery methods.Localized delivery is a promising direction,utilizing the tissue tropism of AAVs to reduce systemic side effects and lower the required viral dose,thus improving targeting and efficiency,especially for organs that are difficult to treat with conventional methods.These innovations have opened new pathways for the clinical application of AAVs.This review aims to provide a comprehensive summary of the various applications of AAVs,offer valuable insights for future research directions,and holds significant importance for researchers and clinicians in the field.As AAV therapy continues to evolve,this article emphasizes its transformative potential in treating genetic diseases,indicating the central role of AAV in the future of gene therapy.
文摘Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or forceps to save the newborn. The purpose of this study was to determine the prevalence of vacuum-assisted vaginal delivery (VAVD) and its associated short-term maternal and neonatal outcomes at Ndola Teaching Hospital. Methods: A retrospective cross-sectional descriptive study through the analysis of routine data for women with singleton-term pregnancies who delivered by vacuum compared with spontaneous vaginal delivery was done at a tertiary hospital for the years 2020 and 2021. Chi-square and Logistic regression were used to investigate factors of vacuum delivery and to adjust for potential confounders. Results: Results showed that VAVD was mostly performed in women who had delayed second stage of labour (25.4%), maternal exhaustion (16.0%), foetal distress in the second stage of labour (12.3%). The overall VAVD prevalence was 3.7% (581/15591). Logistic regression showed that multiparous women were noted to be 87.5% (aOR 0.125;95% CI 0.025 - 0.629;p = 0.012) less likely to undergo VAVD compared to nulliparous women. Registrars were almost 6 times (aOR 5.650;95% CI 1.458 - 22.222, p = 0.012) more likely to conduct VAVD compared to midwives. Episiotomy was 3 times (aOR 3.390;95% CI 1.185 - 9.524;p Conclusion: The findings indicate the underutilisation of VAVD at NTH based on the low prevalence of 3.7%. VAVD outcomes were affected by multiparity, skill level and Episiotomy procedure, in addition, VAVD influenced admission to the NICU. Hence, there is a need to increase skills in VAVD among first-line healthcare workers such as midwives and intern doctors.
文摘Effective therapeutic intervention for central nervous system(CNS)diseases,including brain tumors and neurodegenerative disorders,is significantly challenged by the formidable blood-brain barrier(BBB).This biological barrier severely restricts the passage of most drug candidates,resulting in inefficient delivery to pathological sites and substantially contributing to high clinical trial failure rates for CNS therapies.Engineered nanoparticles have emerged as promising functional material systems capable of navigating these delivery obstacles,offering advantages like encapsulating diverse agents,controlled release,and targeted delivery.This review comprehensively analyzes innovative nanoparticle strategies specifically designed to overcome the BBB and achieve precise CNS delivery via systemic administration.We highlight the critical multi-step biological cascade required for successful therapeutic outcomes:maintaining colloidal stability in circulation,efficiently penetrating the BBB,achieving specific accumulation at the disease site,and effectively engaging target cells.Despite significant advancements,clinical translation of these nanoparticle systems remains limited.A thorough understanding of this multi-step process is paramount to accelerating the clinical application of brain-targeted nanomedicines.
基金supported by the Fundamental Research Funds for the Central Universities(2024JBZX038)the National Natural Science Foundation of China(62076023).
文摘With the rapid development of low-altitude economy and unmanned aerial vehicles (UAVs) deployment technology, aerial-ground collaborative delivery (AGCD) is emerging as a novel mode of last-mile delivery, where the vehicle and its onboard UAVs are utilized efficiently. Vehicles not only provide delivery services to customers but also function as mobile ware-houses and launch/recovery platforms for UAVs. This paper addresses the vehicle routing problem with UAVs considering time window and UAV multi-delivery (VRPU-TW&MD). A mixed integer linear programming (MILP) model is developed to mini-mize delivery costs while incorporating constraints related to UAV energy consumption. Subsequently, a micro-evolution aug-mented large neighborhood search (MEALNS) algorithm incor-porating adaptive large neighborhood search (ALNS) and micro-evolution mechanism is proposed. Numerical experiments demonstrate the effectiveness of both the model and algorithm in solving the VRPU-TW&MD. The impact of key parameters on delivery performance is explored by sensitivity analysis.
基金supported by the grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
基金supported by the National Natural Science Foundation of China(82204634,82174047,81622051)the Zhejiang Provincial Natural Science Foundation of China(LQ22H280010)the Foundation of Zhejiang Chinese Medical University(2021ZR03).
文摘Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
基金supported by National Natural Science Foundation of China(82104082)Natural Science Foundation of Qinghai Province(2024-ZJ-911).
文摘The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed.Beyond these vectors,polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities,such as improving the stability,cellar uptake and endosomal escape of nucleic acid drugs,along with precise delivery to targeted tissues.This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery,focusing on key cationic polymers,nanocarrier types,and preparation methods.It also highlights targeted diseases,strategies to improve delivery efficiency,and potential future directions in this research area.The review is hoped to inspire the development,optimization,and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.
基金supported by the Committee of Science of the Ministry of Education and Science of the Republic of Kazakhstan under Grant No.249015/0224.
文摘Unmanned aerial vehicles(UAVs)are widely used in situations with uncertain and risky areas lacking network coverage.In natural disasters,timely delivery of first aid supplies is crucial.Current UAVs face risks such as crashing into birds or unexpected structures.Airdrop systems with parachutes risk dispersing payloads away from target locations.The objective here is to use multiple UAVs to distribute payloads cooperatively to assigned locations.The civil defense department must balance coverage,accurate landing,and flight safety while considering battery power and capability.Deep Q-network(DQN)models are commonly used in multi-UAV path planning to effectively represent the surroundings and action spaces.Earlier strategies focused on advanced DQNs for UAV path planning in different configurations,but rarely addressed non-cooperative scenarios and disaster environments.This paper introduces a new DQN framework to tackle challenges in disaster environments.It considers unforeseen structures and birds that could cause UAV crashes and assumes urgent landing zones and winch-based airdrop systems for precise delivery and return.A new DQN model is developed,which incorporates the battery life,safe flying distance between UAVs,and remaining delivery points to encode surrounding hazards into the state space and Q-networks.Additionally,a unique reward system is created to improve UAV action sequences for better delivery coverage and safe landings.The experimental results demonstrate that multi-UAV first aid delivery in disaster environments can achieve advanced performance.
基金supported by the National Natural Science Foundation of China(No.52105072)Zhejiang Provincial Natural Science Foundation of China(No.LZ24E050004)+2 种基金Jiangsu Provincial Outstanding Youth Program(No.BK20230072)a grant from Suzhou Industrial Foresight and Key Core Technology Project(No.SYC2022044)grants from Jiangsu Qinglan Project and Jiangsu 333 High-level Talents.
文摘Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,limitations in space and energy supply have resulted in the inability to perform multiple diagnostic and treatment tasks using a single capsule.In this study,we developed a dual-functional capsule robot(DFCR)for drug delivery and tissue biopsy based on magnetic torsion spring technology.The delivery module was shown to rotate the push rod with a thrust of 894 mN to release approximately 0.3 mL of semisolid drug.The biopsy module used a built-in blade to cut tissue with a shear stress of 22.87 MPa,producing a sample of approximately 1.8 mm3.Additionally,a five-degree-of-freedom permanent magnet drive system was developed.By adjusting the strength of the unidirectional magnetic field generated by an external magnet,the capsule can be wirelessly controlled to sequentially trigger the two functions.Ex vivo tests on porcine stomachs confirmed the feasibility of the prototype capsule(12 mm in diameter and 45 mm in length)in active movement,medication,and tissue biopsy.The newly developed DFCR further expands the clinical application prospects of WCE robots in minimally invasive surgery.
基金supported by the National Natural Science Foundation of China(51925304)Natural Science Foundation of Sichuan Province(2024NSFSC1023)Medical Research Program of Sichuan Province(Q23015).
文摘Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.
文摘Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.
文摘Four glycoluril-based amphiphilic molecular clips(AMCs)M1~M4 have been prepared for intracellular delivery of short DNA.M1~M4 have two methyl groups on its convex surface and four cations on its aromatic side arm,which can be used to construct self-assembled nanoparticles in aqueous solution driven by hydrophobic interaction.Dynamic light scattering experiments show that M1 and M2 can be driven hydrophobically to aggregate into extremely stable nanoparticles in water at the micromolar concentrations.Fluorescence titration and zeta potential experiments support that the nanoparticles formed by M1 and M2 are able to efficiently encapsulate short DNA(sDNA).Fluorescence imaging and flow cytometry studies reveal that their nano sizes enable intracellular delivery of the encapsulated sDNA into both normal and cancer cells,with delivery percentage reaching up to 94%,while in vitro experiments indicate that the two compounds have excellent biocompatibility and low cytotoxicity.
基金supported by a grant from The National Natural Science Foundation of China(32000997)。
文摘Spores and pollen,as ubiquitous organisms found in nature,possess a remarkable core-shell structure and intricate surface morphology.These tiny particles are notable for their dimensional uniformity,sustainable utilization,environmental friendliness,porosity,amphiphilicity,and strong adhesive properties.In addition,they display excellent biocompatibility and biodegradability,which significantly enhances the stability and targeting of drugs within the body.Spores and pollen can be extracted using methods such as acidic solutions,alkaline solutions,or enzyme treatments to obtain sporopollenin,which is an extremely resilient and chemically inert complex biopolymer.The sporopollenin extracted through this process removes the original bioactive substances,such as cell nuclei,enzymes,and DNA,providing greater drug loading capacity and containing no potential allergens or immunogens,thus further enhancing its drug loading capacity and improving safety in therapeutic applications.Due to these beneficial attributes,spores,pollen and sporopollenin have gained widespread use in a variety of drug delivery systems,such as targeted delivery,sustained drug delivery,toxicity mitigation,flavor masking,vaccine delivery,delivery of labile substances,and other applications.This review introduces the types of natural spores and pollen commonly used in drug delivery systems,including their main components,common effects,and uses in drug delivery systems,and so on.It subsequently summarizes novel optimization methods in their processing,such as physical treatment,surface modification,and chemical modification,which enable higher drug loading efficiency,stability,and targeting,among other benefits.Additionally,this paper reviews the research progress and applications of natural spores,pollen,and sporopollenin in drug delivery systems,while also touching on some innovative research content,such as novel nanomotor microcarriers developed based on pollen.Based on these research findings,we further elaborate on the advantages of spores,pollen,and sporopollenin in drug delivery systems.For example,they have high stability and drug loading capacity,good adhesion,excellent targeting,and are easy to modify functionally.Currently,they show promising prospects in the fields of targeted drug delivery,sustained-release drug delivery,as well as the delivery of drugs that are effective but slightly toxic,and are often used in research on the treatment of diseases such as cancer and inflammation.We have also highlighted the challenges they face in various applications and identified some issues that need to be addressed,including difficulties in largescale production,the need to improve extraction and purification processes,and the existence of a low but still noteworthy risk of allergies,in order to fully leverage their potential in drug delivery applications.According to current research,although spores,pollen,and sporopollenin face some unresolved issues in clinical drug delivery,they still have great potential overall and are expected to become a new generation of green drug delivery platforms.In the future,further research into their unique physical and chemical properties and structural characteristics will help develop more efficient and stable drug delivery systems to meet diverse treatment needs.We believe that continued exploration of natural spores,pollen,and sporopollenin will drive this emerging field to achieve continuous breakthroughs and progress,ultimately making an important contribution to the cause of human health.
基金supported by the National Natural Science Foundation of China(Grant number 82074031)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(Grant number TP2020054)+1 种基金Shanghai Sailing Program(21YF1447400)the Program for Shanghai High-Level Local University Innovation Team(SZY20220315).
文摘Microneedle-mediated drug delivery systems(MDDS)have experienced robust growth in recent years,with designers leveraging their creativity to apply these systems for direct drug delivery to the skin,mucous membranes,blood vessel walls and even internal organs.In order to achieve precise drug delivery,various delicately conceived drug release modes based on MDDS have been developed.Herein,to elucidate the design concepts of numerous reported MDDS,we have categorized them into two levels(Level-ⅠMDDS and Level-ⅡMDDS)depending on whether nanoscale and microscale carriers are integrated within the microneedles.In this work,the design strategies of MDDS,as well as the current status of their applications in targeted and intelligent drug delivery were reviewed,while their prospects and challenges for future industrialization and clinical applications were also discussed.
文摘BACKGROUND The rising global burden of liver diseases,such as non-alcoholic fatty liver disease and liver fibrosis,has necessitated innovative therapeutic approaches.Plant-based therapies,recognized for their anti-inflammatory and antioxidant properties,have shown promising effects.However,poor bioavailability limits their clinical application.AIM To map global research trends,key contributors,and emerging themes in plant-based therapies combined with advanced drug delivery systems for liver health.METHODS Using the Scopus database,645 documents were retrieved and analyzed using bibliometric tools Biblioshiny and VOSviewer.Analysis focused on publication trends,geographical contributions,and advancements in drug delivery technologies,including nanoparticles,liposomes,and polymeric micelles.Metrics such as publication growth rate,authorship collaboration,and thematic clustering were assessed.RESULTS The dataset spans 43 years(1981-2024),with an annual growth rate of 11.09%in the number of publications.Research output is dominated by China(33%),followed by the United States(24%)and India(18%).Collaborative studies accounted for 24.34%of publications,with an average of 5.81 co-authors per document.Key innovations include nanoparticle encapsulation of curcumin and silymarin,improving bioavailability by up to 85%.Highly cited studies demonstrated the antioxidant,anti-inflammatory,and anti-fibrotic properties of these compounds.For instance,curcumin nanoparticles showed a 70%improvement in solubility,and silymarin liposomal formulations enhanced therapeutic efficiency by 62%.Thematic analysis revealed a transition from basic clinical observations to molecular and pharmacokinetic research,with a focus on oxidative stress mitigation and hepatoprotection.CONCLUSION This study highlights the growing synergy between plant-based therapies and advanced drug delivery systems,with significant contributions from Asian and Western countries.Future efforts should prioritize clinical trials,standardization of plant extract formulations,and interdisciplinary approaches to maximize therapeutic outcomes.The findings provide a foundation for integrating plant-derived compounds into evidence-based hepatological therapies,addressing critical challenges in bioavailability and safety.
基金supported by the Bridging Grant from Universiti Sains Malaysia (R501LR-RND003–0000001319–0000)funding through the Fundamental Research Grant Scheme (FRGS/1/2020/TK0/USM/02/32–6171275) awarded by the Ministry of Higher Education Malaysia
文摘Current treatments for glioblastoma face challenges such as the blood-brain barrier and lack of targeted therapy,compounded by the aggressive nature,high invasiveness,and heterogeneity of the disease.Exosomes,a subtype of extracellular vesicles are emerging as promising nanocarrier drug delivery systems to address these limitations.Exosomes released by all cell types can be easily obtained and modified as delivery vehicles or therapeutic agents.A systematic review was conducted to evaluate various methods for exosome isolation,characterization,engineering or modification,drug loading and delivery efficiency,including exosome biodistribution and treatment efficacy.A search of four databases for in vitro and in vivo studies(2000–,2023)identified 6165 records,of which 23 articles were found eligible and included for analyses.Most studies applied ultracentrifugation(UC)for exosomes isolation.Cancer cell lines being the most frequently used source of exosomes,followed by stem cells.The incubation approach was predominantly utilized to modify exosomes for drug loading.In vivo analysis showed that exosome biodistribution was primarily concentrated in the brain region,peaking in the first 6 h and remained moderately high.Compared to native exosomes and untreated control groups,utilizing modified native exosomes(cargo loaded)for treating glioblastoma disease models led to more pronounced suppression of tumor growth and proliferation,enhanced stimulation of immune response and apoptosis,effective restoration of drug chemosensitivity,increased anti-tumor effect and prolonged survival rates.Modified exosomes whether through incubation,sonication,transfection,freeze-thawing or their combination,improve targeted delivery and therapeutic efficacy against glioblastoma.
