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
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
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
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
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
Inflammatory bowel disease(IBD)influences several million people around the globe,with a high prevalence in North America and Europe.Results from the studies about host-gut microbial interactions demonstrated that gut...Inflammatory bowel disease(IBD)influences several million people around the globe,with a high prevalence in North America and Europe.Results from the studies about host-gut microbial interactions demonstrated that gut microbiota plays a critical role in the progression of IBD,and probiotics can significantly improve microflora dysbiosis and inflammatory response caused by intestinal pathogens.However,several limitations existed for the probiotics delivered to the intestine in the free form(non-encapsulated),such as low pH and diverse digestive enzymes in the gastrointestinal tract,etc.To overcome the problems,several probiotic delivery systems were established and verified with effects.Here,the types and applications of probiotics in animal models and clinical studies are first reviewed in this paper.Subsequently,various types of probiotic delivery systems are elaborated,containing the well-known microcapsules and hydrogel delivery systems,and the engineered probiotic delivery systems are also introduced.Furthermore,mechanisms of action associated with probiotics are illustrated,including maintaining gut microbiota barrier balance,modulating the immune response,and alleviating oxidative stress,etc.Finally,we discussed the relative advantages and disadvantages of different encapsulation methods,as well as future trends for further development of probiotic delivery systems with health benefits.展开更多
As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is...As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is maximal cytoreductive surgery(CRS)combined with platinum-based chemotherapy.Compared with intravenous chemotherapy,traditional intraperitoneal(IP)chemotherapy exhibits obvious pharmacokinetic(PK)advantages and systemic safety and has shown significant survival benefits in several clinical studies of OC patients.However,there remain several challenges in traditional IP chemotherapy,such as insufficient drug retention,a lack of tumor targeting,inadequate drug penetration,gastrointestinal toxicity,and limited inhibition of tumor metastasis and chemoresistance.Nanomedicine-based IP targeting delivery systems,through specific drug carrier design with tumor cells and tumor environment(TME)targeting,make it possible to overcome these challenges and maximize local therapy efficacy while reducing side effects.In this review article,the rationale and challenges of nanomedicine-based IP chemotherapies,as well as their in vivo fate after IP administration,which are crucial for their rational design and clinical translation,are firstly discussed.Then,current strategies for nanomedicine-based targeting delivery systems and the relevant clinical trials in IP chemotherapy are summarized.Finally,the future directions of the nanomedicine-based IP targeting delivery system for OC and its peritoneal metastasis are proposed,expecting to improve the clinical development of IP chemotherapy.展开更多
Microneedles(MNs)offer a precise and minimally invasive platform for delivering vaccines and therapeutic agents directly into the skin,leveraging the abundance of tissue-resident immune cells to elicit robust and dura...Microneedles(MNs)offer a precise and minimally invasive platform for delivering vaccines and therapeutic agents directly into the skin,leveraging the abundance of tissue-resident immune cells to elicit robust and durable immune responses.Compared to traditional intramuscular or subcutaneous vaccination methods,MNbased vaccines demonstrate superior patient compliance,enhanced antigen stability,and heightened immunogenicity,positioning them as a promising tool in biomedical applications.This review provides a comprehensive overview of the materials and fabrication techniques used in MN preparation,explores their structural classifications,and examines the role of antigens and adjuvants in optimizing vaccine efficacy.Furthermore,the diverse applications of MN delivery systems in preventing infectious diseases,advancing tumor immunotherapy,and addressing other immune-related conditions are discussed.展开更多
Nanoscale drug delivery systems(nano-DDSs)have attracted intense interest in tumor chemotherapy in the last decades,to improve antitumor efficacy and minimize toxic and side effects.As a versatile supramolecular build...Nanoscale drug delivery systems(nano-DDSs)have attracted intense interest in tumor chemotherapy in the last decades,to improve antitumor efficacy and minimize toxic and side effects.As a versatile supramolecular building block,cyclodextrins(CDs)have been widely used in the fabrication of the smart nano-DDSs.Besides their multifunctionality,which makes them versatile core in the star(co)polymers for micellar nanomedicines,specific host-vip inclusion complexation via their hydrophobic cavities endows them diversified functions:(i)design of amphiphilic copolymers for micellar nanomedicines,(ii)supramolecular hydrogels and poly(pseudo)rotaxane nano-hydrogels as drug carriers,and(iii)recipient for direct and indirect drug-loading.In the present work,the recent progress of CDs in nano-DDSs for tumor chemotherapy was reviewed,classified by the crucial roles of CD units.Based on the structureperformance relationship,the future perspective was also proposed.展开更多
Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge si...Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the bloodbrain barrier.In this study,an exosome-membrane(EM)and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain.Histidine/arginine-linked polyamidoamine(PHR)was used as a carrier.PHR binds to pDNA by electrostatic interaction.The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex.For glioblastoma targeting,T7 peptide was attached to the pDNA/PHR-EM complex.Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM(pDNA/PHREM-T7)had a surface charge of–5 mV and a size of 280 nm.Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHREM.Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo.pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM.As a result,the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups.Therefore,the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.展开更多
The integration of RNA interference(RNAi)technology with nanotechnology shows significant potential in overcoming the limitations of traditional double-stranded RNA(dsRNA)delivery systems,thereby enabling more efficie...The integration of RNA interference(RNAi)technology with nanotechnology shows significant potential in overcoming the limitations of traditional double-stranded RNA(dsRNA)delivery systems,thereby enabling more efficient dsRNA delivery.Nanoparticles for dsRNA delivery have the potential to enhance the efficiency of RNAi and improve system stability.In this study,we discuss the limitations of conventional RNAi-based biopesticides,systematically introduce common nanoparticle carriers used for RNA pesticide delivery,analyze the interactions between nanoparticles and dsRNA during the delivery,and finally emphasize the overall limitations,associated risks,and challenges in practical applications.展开更多
Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transderm...Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transdermal patches,and microneedles,are being investigated for their potential to deliver anti-allergy drugs.Purpose of review The review reveals the likely improvements by applying new drug delivery systems,including nanocarriers,transdermal patches and microneedles.Recent findings These new drug delivery systems utilize local administration and do not undergo metabolism pathways in the liver.Thus,they demonstrate high drug targeting,rapid onset action,precise dosage control,and minimal side effects.Limitations on large-scale production and high costs hinder the application of advanced drug delivery systems.Fortunately,forthcoming innovation and maturation will likely overcome the barriers and enable general patients to access anti-allergy drugs delivered by these advanced drug delivery systems,resulting in optimal body functions for everyday life.Conclusion Despite their limitations,new drug delivery systems are still promising solutions for delivering anti-allergy drugs due to their enhanced drug concentration,shortened onset time,and reduced systemic side effects.展开更多
In this article,we revisit an article,which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells(MSCs)for targeted delivery of gemcitabine in pancreatic cancer trea...In this article,we revisit an article,which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells(MSCs)for targeted delivery of gemcitabine in pancreatic cancer treatment.The experimental results demonstrated that the exosome-based drug delivery system derived from MSCs significantly augmented apoptosis in pancreatic cancer cells.The biocompatibility,targeting specificity,and low immunogenicity of exosomes render them as optimal carriers for drug delivery,enabling precise administration of therapeutics to diseased tissues while mitigating adverse effects,thereby achieving targeted treatment of cancer cells and significantly enhancing anti-tumor efficacy.However,the clinical application of exosome drug delivery platforms in oncology still presents challenges,necessitating further optimization to ensure their stability and efficacy.This study focuses on elucidating the advantages of exosomes as a drug delivery platform,exploring the utilization of MSC-derived exosomes in oncology therapy,and discussing their potential and future directions in cancer treatment.展开更多
Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the...Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.展开更多
Neuroinflammation,α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease(PD),an incurable movement disorder.The presence of the blood-brain barrier(BBB)impedes the delivery of ther...Neuroinflammation,α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease(PD),an incurable movement disorder.The presence of the blood-brain barrier(BBB)impedes the delivery of therapeutics and makes the design of drug-targeting delivery vehicles challenging.Nanomedicine is designed and has significantly impacted the scientific community.Over the last few decades,to address the shortcomings of synthetic nanoparticles,a new approach has emerged that mimic the physiological environment.Cell membrane-coated nanoparticles have been developed to interact with the physiological environment,enhance central nervous system drug delivery and mask toxic effects.Cell membranes are multifunctional,biocompatible platforms with the potential for surface modification and targeted delivery design.A synchronous design of cell membrane and nanoparticles is required for the cell membrane-based biomimetics,which can improve the BBB recognition and transport.This review summarizes the challenges in drug delivery and how cell membrane-coated nanoparticles can overcome them.Moreover,major cell membranes used in biomedical applications are discussed with a focus on PD.展开更多
Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation...Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs.展开更多
This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical...This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical interventions forbone regeneration,particularly autogenic bone grafts,and discusses the exploration of alternative materials and methods,including allogeneic and xenogeneic bone grafts,synthetic materials,and biodegradable polymers.The objective is to provide a comprehensive understanding of how contemporary DDS can be optimized and integrated with tissue engineering approaches for more effective bone regeneration therapies.The review explained the mechanisms through which DDS enhance bone repair processes,identifies critical factors influencing their efficacy and safety,and offers an overview of current trends and future perspectives in the field.It emphasizes the need for advanced strategies in bone regeneration that focus on precise control of DDS to address bone conditions such as osteoporosis,trauma,and genetic predispositions leading to fractures.展开更多
BACKGROUND Automated insulin delivery(AID)systems have demonstrated benefits in managing patients with type 2 diabetes(T2D),but data are still limited.Moreover,the efficacy and safety of the AID systems in these patie...BACKGROUND Automated insulin delivery(AID)systems have demonstrated benefits in managing patients with type 2 diabetes(T2D),but data are still limited.Moreover,the efficacy and safety of the AID systems in these patients have been inadequately explored by systematic reviews and meta-analyses.AIM To provide a comprehensive understanding of the optimal use of AID in managing insulin-treated outpatients with T2D.METHODS A systematic search of multiple databases and registries,including MEDLINE,Scopus,Web of Science,Cochrane Library,and ClinicalTrials.gov,was conducted from inception to May 15,2025,to identify studies on AID use for outpatients with T2D.The co-primary outcomes were the change in glycated hemoglobin(HbA1c)and continuous glucose monitoring(CGM)metrics.Statistical analyses were conducted using Review Manager Web software with random-effects models and the inverse variance statistical method.The results were presented as mean differences(MDs)or risk ratios(RRs)with 95%CI.RESULTS A total of 15 studies with 28985 participants were identified,including 6 randomized trials(n=748;3 crossover and 3 parallel-group trials)and 9 single-arm studies.All included randomized trials raised some concerns,and the single-arm studies had serious risks of overall bias.Meta-analysis of randomized trials showed that AID is more effective than the control group in lowering HbA1c(MD:-0.89%,95%CI:-1.32 to-0.46,P<0.0001,I2=82%).Compared to control interventions,AID use was linked to a higher percentage of time in range(MD:19.25%,95%CI:11.43-27.06,P<0.00001,I2=74%)and a lower percentage of time above range>10 mmol/L(MD:-19.48%,95%CI:-27.14 to-11.82,P<0.00001,I2=73%);however,time below range remained similar between the two groups.The mean sensor glucose level was lower in the AID group;however,the coefficient of variation of glucose was the same in both groups.AID use also led to a reduction in insulin dose,but this is not a consistent finding across all study designs.The risks of serious adverse events(AEs)and severe hypoglycemia were similar in both groups;however,AID use raised the risk of device deficiency.Single-arm studies with participants using AID systems also demonstrated reductions in HbA1c(ranging from 0.7%to 2.07%)and improvements in CGM metrics,along with acceptable safety data.CONCLUSION Based on short-term study data,the use of AID systems in outpatients with T2D appears to improve glycemic outcomes and CGM metrics,with no significant AEs.Larger and longer-term randomized controlled trials involving diverse populations,along with a cost-benefit analysis,are needed to guide more informed clinical practice decisions.展开更多
Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing fac...Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.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.
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.
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.
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.
基金supported by the 2022 Ningbo Yongjiang Talent Introduction Programme(Young Talent Sub-Project 2022A-158-G)the Zhejiang Provincial Natural Science Foundation of China(LQ23C200005)the Research Startup Fund of Ningbo University(ZX2022000432).
文摘Inflammatory bowel disease(IBD)influences several million people around the globe,with a high prevalence in North America and Europe.Results from the studies about host-gut microbial interactions demonstrated that gut microbiota plays a critical role in the progression of IBD,and probiotics can significantly improve microflora dysbiosis and inflammatory response caused by intestinal pathogens.However,several limitations existed for the probiotics delivered to the intestine in the free form(non-encapsulated),such as low pH and diverse digestive enzymes in the gastrointestinal tract,etc.To overcome the problems,several probiotic delivery systems were established and verified with effects.Here,the types and applications of probiotics in animal models and clinical studies are first reviewed in this paper.Subsequently,various types of probiotic delivery systems are elaborated,containing the well-known microcapsules and hydrogel delivery systems,and the engineered probiotic delivery systems are also introduced.Furthermore,mechanisms of action associated with probiotics are illustrated,including maintaining gut microbiota barrier balance,modulating the immune response,and alleviating oxidative stress,etc.Finally,we discussed the relative advantages and disadvantages of different encapsulation methods,as well as future trends for further development of probiotic delivery systems with health benefits.
基金supported by the National Key R&D Program of China(No.2020YFE0201700)the Liaoning Revitalization Talents Program(No.XLYC1908031)。
文摘As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is maximal cytoreductive surgery(CRS)combined with platinum-based chemotherapy.Compared with intravenous chemotherapy,traditional intraperitoneal(IP)chemotherapy exhibits obvious pharmacokinetic(PK)advantages and systemic safety and has shown significant survival benefits in several clinical studies of OC patients.However,there remain several challenges in traditional IP chemotherapy,such as insufficient drug retention,a lack of tumor targeting,inadequate drug penetration,gastrointestinal toxicity,and limited inhibition of tumor metastasis and chemoresistance.Nanomedicine-based IP targeting delivery systems,through specific drug carrier design with tumor cells and tumor environment(TME)targeting,make it possible to overcome these challenges and maximize local therapy efficacy while reducing side effects.In this review article,the rationale and challenges of nanomedicine-based IP chemotherapies,as well as their in vivo fate after IP administration,which are crucial for their rational design and clinical translation,are firstly discussed.Then,current strategies for nanomedicine-based targeting delivery systems and the relevant clinical trials in IP chemotherapy are summarized.Finally,the future directions of the nanomedicine-based IP targeting delivery system for OC and its peritoneal metastasis are proposed,expecting to improve the clinical development of IP chemotherapy.
基金supported by the National Science Fund for National Natural Science Foundation of China(Grant Nos.22232006,22377127,and 52361145848)Chinese Academy of Sciences(CAS)Project for Young Scientists in Basic Research(Grant No.YSBR-083)+2 种基金the Beijing Nova Program(Grant Nos.20230484352 and 20240484650)Institute of Process Engineering Project for Frontier Basic Research(Grant No.QYJC-2023-05)Progress of Strategy Priority Research Program(Category B)of CAS(Grant No.XDB0520300).
文摘Microneedles(MNs)offer a precise and minimally invasive platform for delivering vaccines and therapeutic agents directly into the skin,leveraging the abundance of tissue-resident immune cells to elicit robust and durable immune responses.Compared to traditional intramuscular or subcutaneous vaccination methods,MNbased vaccines demonstrate superior patient compliance,enhanced antigen stability,and heightened immunogenicity,positioning them as a promising tool in biomedical applications.This review provides a comprehensive overview of the materials and fabrication techniques used in MN preparation,explores their structural classifications,and examines the role of antigens and adjuvants in optimizing vaccine efficacy.Furthermore,the diverse applications of MN delivery systems in preventing infectious diseases,advancing tumor immunotherapy,and addressing other immune-related conditions are discussed.
文摘Nanoscale drug delivery systems(nano-DDSs)have attracted intense interest in tumor chemotherapy in the last decades,to improve antitumor efficacy and minimize toxic and side effects.As a versatile supramolecular building block,cyclodextrins(CDs)have been widely used in the fabrication of the smart nano-DDSs.Besides their multifunctionality,which makes them versatile core in the star(co)polymers for micellar nanomedicines,specific host-vip inclusion complexation via their hydrophobic cavities endows them diversified functions:(i)design of amphiphilic copolymers for micellar nanomedicines,(ii)supramolecular hydrogels and poly(pseudo)rotaxane nano-hydrogels as drug carriers,and(iii)recipient for direct and indirect drug-loading.In the present work,the recent progress of CDs in nano-DDSs for tumor chemotherapy was reviewed,classified by the crucial roles of CD units.Based on the structureperformance relationship,the future perspective was also proposed.
基金supported by the Individual Basic Science&Engineering Research Program(NRF-2022R1A2B5B01001920)through the National Research Foundation,funded by the Ministry of Science and ICT in Korea.
文摘Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the bloodbrain barrier.In this study,an exosome-membrane(EM)and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain.Histidine/arginine-linked polyamidoamine(PHR)was used as a carrier.PHR binds to pDNA by electrostatic interaction.The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex.For glioblastoma targeting,T7 peptide was attached to the pDNA/PHR-EM complex.Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM(pDNA/PHREM-T7)had a surface charge of–5 mV and a size of 280 nm.Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHREM.Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo.pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM.As a result,the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups.Therefore,the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.
基金Tsinghua Shenzhen International Graduate School,and the National Key R&D Program of China,Synthetic Biology Research(2023YFA0913600).
文摘The integration of RNA interference(RNAi)technology with nanotechnology shows significant potential in overcoming the limitations of traditional double-stranded RNA(dsRNA)delivery systems,thereby enabling more efficient dsRNA delivery.Nanoparticles for dsRNA delivery have the potential to enhance the efficiency of RNAi and improve system stability.In this study,we discuss the limitations of conventional RNAi-based biopesticides,systematically introduce common nanoparticle carriers used for RNA pesticide delivery,analyze the interactions between nanoparticles and dsRNA during the delivery,and finally emphasize the overall limitations,associated risks,and challenges in practical applications.
文摘Background Present drug delivery systems such as oral administration and intravenous injection limit the drug efficacy of current anti-allergy drugs.Therefore,new drug delivery systems,including nanocarriers,transdermal patches,and microneedles,are being investigated for their potential to deliver anti-allergy drugs.Purpose of review The review reveals the likely improvements by applying new drug delivery systems,including nanocarriers,transdermal patches and microneedles.Recent findings These new drug delivery systems utilize local administration and do not undergo metabolism pathways in the liver.Thus,they demonstrate high drug targeting,rapid onset action,precise dosage control,and minimal side effects.Limitations on large-scale production and high costs hinder the application of advanced drug delivery systems.Fortunately,forthcoming innovation and maturation will likely overcome the barriers and enable general patients to access anti-allergy drugs delivered by these advanced drug delivery systems,resulting in optimal body functions for everyday life.Conclusion Despite their limitations,new drug delivery systems are still promising solutions for delivering anti-allergy drugs due to their enhanced drug concentration,shortened onset time,and reduced systemic side effects.
基金Natural Science Foundation of Zhejiang Province,No.LQ23H050005Zhejiang Medical and Health Science and Technology Project,No.2023KY615+2 种基金Scientific Research Project of Zhejiang Provincial Education Department,No.Y202250731 and No.Y202353130the China Students’Innovation and Entrepreneurship Training Program,No.202310338044China Postdoctoral Science Foundation,No.2022M721720.
文摘In this article,we revisit an article,which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells(MSCs)for targeted delivery of gemcitabine in pancreatic cancer treatment.The experimental results demonstrated that the exosome-based drug delivery system derived from MSCs significantly augmented apoptosis in pancreatic cancer cells.The biocompatibility,targeting specificity,and low immunogenicity of exosomes render them as optimal carriers for drug delivery,enabling precise administration of therapeutics to diseased tissues while mitigating adverse effects,thereby achieving targeted treatment of cancer cells and significantly enhancing anti-tumor efficacy.However,the clinical application of exosome drug delivery platforms in oncology still presents challenges,necessitating further optimization to ensure their stability and efficacy.This study focuses on elucidating the advantages of exosomes as a drug delivery platform,exploring the utilization of MSC-derived exosomes in oncology therapy,and discussing their potential and future directions in cancer treatment.
基金supported by CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-026,China).
文摘Gliomas are the most common intracranial tumors with poor survival and high mortality.Furthermore,the clinical efficacy of current drugs is still not ideal;despite the development of several therapeutic drugs over the past decades and tumor progression or recurrence is inevitable in many patients.RNAibased therapy presents a novel disease-related gene targeting therapy,including otherwise undruggable genes,and generates therapeutic options.However,the therapeutic effect of siRNA is hindered by multiple biological barriers,primarily the blood-brain barrier(BBB).A glycoprotein-derived peptide-mediated delivery system is the preferred option to resolve this phenomenon.RDP,a polypeptide composed of 15 amino acids derived from rabies virus glycoprotein(RVG),possesses an N-type acetylcholine receptor(nAChR)-binding efficiency similar to that of RVG29.Given its lower cost and small particle size when used as a ligand,RDP should be extensively evaluated.First,we verified the brain-targeting efficacyy of RDP at the cellular and animal levels and further explored the possibility of using the RDP-oligoarginine peptide(designated RDP-5R)as a bio-safe vehicle to deliver therapeutic siRNA into glioma cells in vitro and in vivo.The polypeptide carrier possesses a diblock design composed of oligoarginine for binding siRNA through electrostatic interactions and RDP for cascade BBB-and glioma cell-targeting.The results indicated that RDP-R5/siRNA nanoparticles exhibited stable and suitable physicochemical properties for in vivo application,desirable glioma-targeting effects,and therapeutic efficiency.As a novel and efficient polypeptide carrier,RDP-based polypeptides hold great promise as a noninvasive,safe,and efficient treatment for various brain diseases.
基金Department of Pharmaceuticals,Ministry of Chemicals and Fertilizers,Centre of Excellence(CoE),NDDS,NIPER-Raebareli.Communication Number/737。
文摘Neuroinflammation,α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease(PD),an incurable movement disorder.The presence of the blood-brain barrier(BBB)impedes the delivery of therapeutics and makes the design of drug-targeting delivery vehicles challenging.Nanomedicine is designed and has significantly impacted the scientific community.Over the last few decades,to address the shortcomings of synthetic nanoparticles,a new approach has emerged that mimic the physiological environment.Cell membrane-coated nanoparticles have been developed to interact with the physiological environment,enhance central nervous system drug delivery and mask toxic effects.Cell membranes are multifunctional,biocompatible platforms with the potential for surface modification and targeted delivery design.A synchronous design of cell membrane and nanoparticles is required for the cell membrane-based biomimetics,which can improve the BBB recognition and transport.This review summarizes the challenges in drug delivery and how cell membrane-coated nanoparticles can overcome them.Moreover,major cell membranes used in biomedical applications are discussed with a focus on PD.
基金sponsored by the Fundamental Research Funds forthe Central Universities(No.2024-JYB-JBZD-047)High Level Key Discipline Construction of Traditional Chinese Medicine(zyyzdxk-2023272).
文摘Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs.
文摘This article reviews recent advancements,innovative strategies,and the key challenges in Drug Delivery Systems(DDS)for bone regeneration,focusing on tissue engineering.It highlights the limitations of current surgical interventions forbone regeneration,particularly autogenic bone grafts,and discusses the exploration of alternative materials and methods,including allogeneic and xenogeneic bone grafts,synthetic materials,and biodegradable polymers.The objective is to provide a comprehensive understanding of how contemporary DDS can be optimized and integrated with tissue engineering approaches for more effective bone regeneration therapies.The review explained the mechanisms through which DDS enhance bone repair processes,identifies critical factors influencing their efficacy and safety,and offers an overview of current trends and future perspectives in the field.It emphasizes the need for advanced strategies in bone regeneration that focus on precise control of DDS to address bone conditions such as osteoporosis,trauma,and genetic predispositions leading to fractures.
文摘BACKGROUND Automated insulin delivery(AID)systems have demonstrated benefits in managing patients with type 2 diabetes(T2D),but data are still limited.Moreover,the efficacy and safety of the AID systems in these patients have been inadequately explored by systematic reviews and meta-analyses.AIM To provide a comprehensive understanding of the optimal use of AID in managing insulin-treated outpatients with T2D.METHODS A systematic search of multiple databases and registries,including MEDLINE,Scopus,Web of Science,Cochrane Library,and ClinicalTrials.gov,was conducted from inception to May 15,2025,to identify studies on AID use for outpatients with T2D.The co-primary outcomes were the change in glycated hemoglobin(HbA1c)and continuous glucose monitoring(CGM)metrics.Statistical analyses were conducted using Review Manager Web software with random-effects models and the inverse variance statistical method.The results were presented as mean differences(MDs)or risk ratios(RRs)with 95%CI.RESULTS A total of 15 studies with 28985 participants were identified,including 6 randomized trials(n=748;3 crossover and 3 parallel-group trials)and 9 single-arm studies.All included randomized trials raised some concerns,and the single-arm studies had serious risks of overall bias.Meta-analysis of randomized trials showed that AID is more effective than the control group in lowering HbA1c(MD:-0.89%,95%CI:-1.32 to-0.46,P<0.0001,I2=82%).Compared to control interventions,AID use was linked to a higher percentage of time in range(MD:19.25%,95%CI:11.43-27.06,P<0.00001,I2=74%)and a lower percentage of time above range>10 mmol/L(MD:-19.48%,95%CI:-27.14 to-11.82,P<0.00001,I2=73%);however,time below range remained similar between the two groups.The mean sensor glucose level was lower in the AID group;however,the coefficient of variation of glucose was the same in both groups.AID use also led to a reduction in insulin dose,but this is not a consistent finding across all study designs.The risks of serious adverse events(AEs)and severe hypoglycemia were similar in both groups;however,AID use raised the risk of device deficiency.Single-arm studies with participants using AID systems also demonstrated reductions in HbA1c(ranging from 0.7%to 2.07%)and improvements in CGM metrics,along with acceptable safety data.CONCLUSION Based on short-term study data,the use of AID systems in outpatients with T2D appears to improve glycemic outcomes and CGM metrics,with no significant AEs.Larger and longer-term randomized controlled trials involving diverse populations,along with a cost-benefit analysis,are needed to guide more informed clinical practice decisions.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82304443,82030107,and 82373944).
文摘Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.
