The use of microneedles(MNs)has been established as an effective transdermal drug delivery strategy that has been extensively deployed for treating various diseases,including skin diseases.MNs can surpass the constrai...The use of microneedles(MNs)has been established as an effective transdermal drug delivery strategy that has been extensively deployed for treating various diseases,including skin diseases.MNs can surpass the constraints of conventional drug delivery methods by their superior safety and efficacy through precise targeting,while simultaneously enabling painless delivery.Currently,MNs are increasingly used as carriers for drug delivery,with the loading of insoluble drugs to improve their treatment efficiency or combining with bioactive substances for the construction of an efficient drug delivery system to maximize the effects of bioactive substances.The methods used for preparation MNs are diverse,enabling them to meet the requirements of most applications.The emergence of MNs has addressed the shortcomings associated with insoluble drugs,expanded the applications of bioactive substances,and improved their use in clinical practice.This review summarizes current information on the application of MNs in a variety of skin diseases,such as psoriasis,vitiligo,alopecia,hypertrophic scarring,atopic dermatitis,melanoma,acne,and skin infections.The current clinical applications and future opportunities for MNs in the treatment of skin diseases are also discussed.Despite substantial progress in the clinical application of MNs as delivery vectors,issues such as low drug loading and poor mechanical strength during MNs preparation remain the main challenges.Therefore,clinical implementation of MNs-based therapies remains limited,highlighting key opportunities for future research.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
Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,con...Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,conventional MNs employ long needles(≥600μm),leading to pain and skin irritation.Moreover,it is critical to stably apply MNs against complex skin surfaces for uniform nanoscale drug delivery.Herein,a dually amplified transdermal patch(MN@EV/SC)is developed as the stem cell-derived EV delivery platform by hierarchically integrating an octopusinspired suction cup(SC)with short MNs(≤300μm).While leveraging the suction effect to induce nanoscale deformation of the stratum corneum,MN@EV/SC minimizes skin damage and enhances the adhesion of MNs,allowing EV to penetrate deeper into the dermis.When MNs of various lengths are applied to mouse skin,the short MNs can elicit comparable corticosterone release to chemical adhesives,whereas long MNs induce a prompt stress response.MN@EV/SC can achieve a remarkable penetration depth(290μm)for EV,compared to that of MN alone(111μm).Consequently,MN@EV/SC facilitates the revitalization of fibroblasts and enhances collagen synthesis in middle-aged mice.Overall,MN@EV/SC exhibits the potential for skin regeneration by modulating the dermal microenvironment and ensuring patient comfort.展开更多
Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold ...Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold molding process with 20%w/v poly-vinylpyrrolidone and 15%w/v polyvinyl alcohol.The SFA-MNs were assessed for morphology,mechanical properties,in vitro dissolution,identification of components,and skin lesion improvement in imiquimod-induced psoriasis mice.Results:The SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis,facilitating efficient drug delivery.Furthermore,they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differ-entiation 3 and tumor necrosis factor-a.In addition,this system alleviated skin inflammation,splenic swelling,and thymic atrophy in the psoriasis-like mouse model.Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios(m/z)of the secondary fragments N-methylcytisine,5a,9a-dihydroxymatrine,sophoramine,matrine,oxysophocarpine,oxymatrine,and kushenol O.Conclusion:The drug delivery strategy combining traditional herbal S.flavescens with soluble micro-needle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models,enabling enhanced therapeutic effects compared with the control group.展开更多
Rapidly-advancing microneedle-based bioelectronics integrated with electrical stimulation(ES)therapy exhibit significant potential for improving chronic wound management.Herein,bio-inspired by the serrated structure o...Rapidly-advancing microneedle-based bioelectronics integrated with electrical stimulation(ES)therapy exhibit significant potential for improving chronic wound management.Herein,bio-inspired by the serrated structure of bee-stingers,we developed a temperature-sensitive,two-stage microneedle-based electro active platform(GP-PPy/PLA-MN)featuring rivet-like micros tructures that integrates intelligent,precise drug-releasing,ES-transmission,and real-time wound-assessment monitoring for comprehensive chronic wound-management and diagnostic therapy.The bionic-design mechanically anchors the microneedle beneath the skin's dermis,while GP-PPy/PLA-MN demonstrates versatile therapeutic characteristics,including outstanding biocompatibility,antimicrobial properties,and antimigratory origins.The GP-PPy/PLA-MN enables the sustained release of insulin at body temperature for up to24 hours through the poly-N-isopropyl acrylamide grafted amidated-gelatin-based thermo-sensitive hydrogel at the needle-tip,thereby providing long-term stable blood glucose control.GP-PPy/PLA-MN indicates its potential as a novel bioelectronics-based patch to record the temperature and humidity during the wound-healing process,realizing significant wound diagnosis and real-time wound assessment,and fundamentally facilitating the therapeutic efficacy by supplying solid data to protect the clinical practice.Extensive in vitro and in vivo studies have demonstrated that GP-PPy/PLA-MN can provide effective ES and sustained drug release,thereby promoting chronic wound healing and increasing the wound healing rate by 20%compared to the control group after 14 days of treatment.This innovative approach combines bioelectronics with intelligent drug delivery and microneedling technology to effectively address the critical challenges of chronic wound management,offering promising prospects for precision diagnostics and therapeutic interventions.展开更多
Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical...Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin interstitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50%.In the concentration range of 1×10_(7) to 1×10^(10) colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87%.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.展开更多
Nanoparticles-incorporated hydrogel microneedles(NPs-HMN)have attracted significant attention due to their exceptional biomedical applications.The arrayed needle tips of NPsHMN effectively penetrate the skin or tissue...Nanoparticles-incorporated hydrogel microneedles(NPs-HMN)have attracted significant attention due to their exceptional biomedical applications.The arrayed needle tips of NPsHMN effectively penetrate the skin or tissue,enabling minimally invasive and painless delivery of therapeutic molecules into the tissue microenvironment.This approach has shown significant improvements in bioavailability and patient compliance.Moreover,the functionalized hydrogel materials of NPs-HMN exhibit a three-dimensional network structure resembling the extracellular matrix,along with controllable drug release,exceptional swelling ability,hydrophilicity,and biocompatibility.These characteristics broaden the potential applications of HMN in therapeutic and biosensing contexts.In addition,the incorporation of nanoparticles(NPs)has been shown to improve the solubility of hydrophobic drugs,enhance mechanical properties,enable intelligent drug release,and facilitate precise targeting of HMN.The versatility and diversity of treatment options afforded by NPs-HMN contribute to significant advancements in animal models and clinical settings,as well as offer valuable insights for biomaterial development.This review provides a comprehensive examination of the fabrication strategies of NPs-HMN and their recent advancements in biomedical applications.We also analyze the mechanisms,advantages,challenges,and future prospects of this system in enhancing drug delivery efficiency to provide theoretical references for further breakthroughs in novel delivery platforms.展开更多
Microneedle(MN)is a medical device containing an array of needles with a micrometer-scale.It can penetrate the human stratum corneum painlessly and efficiently for treatment and diagnosis purposes.Currently,the materi...Microneedle(MN)is a medical device containing an array of needles with a micrometer-scale.It can penetrate the human stratum corneum painlessly and efficiently for treatment and diagnosis purposes.Currently,the materials commonly used to manufacture MNs include silicon,polymers,ceramics and metals.Metallic MNs(MMNs)have drawn significant attention owing to its superior mechanical properties,machinability,and biocompatibility.This paper is a state-of-the-art review of the structure,fabrication technologies,and applications of MMNs.According to the relative position of the axis of MN and the plane of the substrate,MMNs can be divided into in-plane and out-of-plane.Solid,hollow,coated and porous MMNs are also employed to characterize their internal and surface structures.Until now,numerous fabrication technologies,including cutting tool machining,non-traditional machining,etching,hot-forming,and additive manufacturing,have been used to fabricate MMNs.The recent advances in the application of MMNs in drug delivery,disease diagnosis,and cosmetology are also discussed in-depth.Finally,the shortcomings in the fabrication and application of MMNs and future directions for development are highlighted.展开更多
Objective:Microneedles(MNs),as a key component of third-generation transdermal drug delivery sys-tems,show strong potential for obesity treatment.This study aimed to integrate traditional Chinese medicine(TCM)therapie...Objective:Microneedles(MNs),as a key component of third-generation transdermal drug delivery sys-tems,show strong potential for obesity treatment.This study aimed to integrate traditional Chinese medicine(TCM)therapies,including Chinese patent medicine(CPM)injections and patches,with MN technology to identify commonly used administration sites and Chinese medicinal material(CMM)con-stituents suitable for MN-based weight loss interventions.Methods:Literature was retrieved from PubMed,Web of Science,Google Scholar,CNKI,and Google Patents.First,existing studies on MN-based weight loss were narratively reviewed.Then,studies on CPM injections or patches were analyzed to extract intervention elements,including administration sites,CMM constituents,and symptoms.Acupoint-symptom and CMM constituent-symptom pairs were compiled,and key nodes were identified through complex network analysis using eigenvector centrality,PageRank,and betweenness centrality.Results:Forty-four studies and thirteen patents were included.The review indicated that MN-based in-terventions demonstrated significant weight loss effects;however,current research remains limited by a focus on fat-deposition sites and insufficient development of CMM carriers.Network analysis identi-fied Guanyuan(CV4)and Poria cocos(Fuling)as central nodes across all metrics,suggesting their strong potential as key elements in MN-based therapies.Conclusion:CV4 and Poria cocos represent promising candidates for delivery sites and CMM constituents in MN-mediated obesity treatment.By integrating TCM principles with modern MN technology,these findings provide a theoretical basis for developing more targeted,efficient,and integrative anti-obesity interventions.展开更多
Microneedles(MNs)have attracted increasing attention as a transdermal delivery system(TDDS)[1].However,traditional volatile Chinese medicines cannot be dissolved in conventional soluble MN materials,such as hyaluronic...Microneedles(MNs)have attracted increasing attention as a transdermal delivery system(TDDS)[1].However,traditional volatile Chinese medicines cannot be dissolved in conventional soluble MN materials,such as hyaluronic acid and chitosan,making it difficult for many traditional Chinese medicine ingredients to be applied to MN.Elemene(ELE)was successfully isolated from Curcuma longa,and has numerous antitumor and curative effects[2].展开更多
Microneedles(MNs)are an innovative and viable option for drug delivery that offer the distinct advantages of minimal invasiveness,painlessness,stable drug loading,efficient drug permeation,and biocompatibility.MNs wer...Microneedles(MNs)are an innovative and viable option for drug delivery that offer the distinct advantages of minimal invasiveness,painlessness,stable drug loading,efficient drug permeation,and biocompatibility.MNs were first used to penetrate the skin surface and facilitate transcutaneous drug delivery with great success.Recent applications of MNs have extended to non-transdermal drug delivery,specifically,to various tissues and organs.This review captures the fabrication methods for MNs,discusses advanced design strategies for achieving controlled drug release,and summarizes current MN applications in delivering multiple therapeutic agents to the cardiovascular,digestive(e.g.,oral cavity),reproductive,and central nervous systems.The findings in this review would contribute toward the improved designs of MN systems that can be modified according to purpose,including material selection,structural design,choice of fabrication methods,and tissue considerations,to determine the optimal therapeutic regimen for the target treatment area.展开更多
Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of tran...Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.展开更多
Myocardial infarction(MI)is a challenging condition that results in scar formation on the ventricular wall,causing myocardial damage and ventricular thinning.Engineered cardiac patches(ECPs)designed to regenerate myoc...Myocardial infarction(MI)is a challenging condition that results in scar formation on the ventricular wall,causing myocardial damage and ventricular thinning.Engineered cardiac patches(ECPs)designed to regenerate myocardial tissue have been proposed to repair the ventricular wall and replenish myocardial cells.However,their clinical use is limited by manufacturing and fixation challenges.This study introduces a manufacturing strategy for a composite ECP,which comprises an antiadhesion shell layer,a conductive myocardial tissue,and an exosome-laden microneedle substrate.The ECP can anchor to the infarcted myocardium through its microneedle substrate.Meanwhile,its outer shell prevents nonspecific adhesion,enabling stable and suture-free attachment.Using this microneedle substrate,we applied a 3D-printed ECP in a rat model of post-MI repair.Our results showed that this strategy reduced left ventricular damage,improved cardiac ejection fraction,decreased the fibrotic area,increased ventricular wall thickness,improved microvascular recovery,and thus facilitated the repair of maladaptive ventricular remodeling post-MI.This microneedle substrate holds great promise for use in the fixation of patches during the repair of myocardial tissue and other organs,thereby promoting the clinical application of tissue-engineered patches.展开更多
Chronic diabetic wounds result from a disrupted microenvironment where oxidative stress,impaired angiogenesis,and persistent infection create a vicious cycle that delays healing.Unfortunately,existing treatments often...Chronic diabetic wounds result from a disrupted microenvironment where oxidative stress,impaired angiogenesis,and persistent infection create a vicious cycle that delays healing.Unfortunately,existing treatments often fail to address these interrelated issues,resulting in suboptimal healing.Here,we propose a base-tip dual-component hydrogel microneedle(MN)system(GBEVs-pVEGF/AgNPs@MNs),consisting of a tip loaded with plant-bacterial hybrid extracellular vesicles(GBEVs-pVEGF)and a base containing silver nanoparticles(AgNPs).Upon penetrating the necrotic tissue of diabetic wounds,our multifunctional MNs could effectively deliver GBEVs-pVEGF,thereby alleviating oxidative stress,promoting cell migration,and facilitating angiogenesis.Additionally,the physical barrier formed by the basal layer synergistically mitigates persistent bacterial infections during wound healing in conjunction with the antimicrobial agent AgNPs.This multifunctional MN system,integrating antioxidant,angiogenic,and antimicrobial properties,effectively restores the disrupted wound microenvironment,offering significant potential for accelerating diabetic wound healing.展开更多
Delayed or non-healing of diabetic wounds is a significant complication,often attributed to high glucose-induced M1 macrophage accumulation,impaired angiogenesis,and reactive oxygen species(ROS)buildup.Addressing this...Delayed or non-healing of diabetic wounds is a significant complication,often attributed to high glucose-induced M1 macrophage accumulation,impaired angiogenesis,and reactive oxygen species(ROS)buildup.Addressing this,we introduced a strontium polyphenol network microneedle patch(SrC-MPNs@MN-PP)for percutaneous drug delivery.This patch,formulated with polymer poly(γ-glutamic acid)(γ-PGA)and epsilon-poly-l-lysine(ε-PLL),incorporates strontium polyphenol networks(SrC-MPNs).The release of chlorogenic acid(CGA)from SrC-MPNs not only neutralizes ROS,but strontium ions also foster angiogen-esis.Consequently,SrC-MPNs@MN-PP can ameliorate the diabetic wound microenvironment and expedite healing.展开更多
Flexible pressure sensors have many potential applications in the monitoring of physiological signals because of their good biocompatibil-ity and wearability.However,their relatively low sensitivity,linearity,and stab...Flexible pressure sensors have many potential applications in the monitoring of physiological signals because of their good biocompatibil-ity and wearability.However,their relatively low sensitivity,linearity,and stability have hindered their large-scale commercial application.Herein,aflexible capacitive pressure sensor based on an interdigital electrode structure with two porous microneedle arrays(MNAs)is pro-posed.The porous substrate that constitutes the MNA is a mixed product of polydimethylsiloxane and NaHCO3.Due to its porous and interdigital structure,the maximum sensitivity(0.07 kPa-1)of a porous MNA-based pressure sensor was found to be seven times higher than that of an imporous MNA pressure sensor,and it was much greater than that of aflat pressure sensor without a porous MNA structure.Finite-element analysis showed that the interdigital MNA structure can greatly increase the strain and improve the sensitivity of the sen-sor.In addition,the porous MNA-based pressure sensor was found to have good stability over 1500 loading cycles as a result of its bilayer parylene-enhanced conductive electrode structure.Most importantly,it was found that the sensor could accurately monitor the motion of afinger,wrist joint,arm,face,abdomen,eye,and Adam’s apple.Furthermore,preliminary semantic recognition was achieved by monitoring the movement of the Adam’s apple.Finally,multiple pressure sensors were integrated into a 33 array to detect a spatial pressure distribu-×tion.Compared to the sensors reported in previous works,the interdigital electrode structure presented in this work improves sensitivity and stability by modifying the electrode layer rather than the dielectric layer.展开更多
Investigation of patient-derived primary tissues is of great importance in the biomedical field,but recent tissue slicing and cultivation techniques still have difficulties in satisfying clinical requirements.Here,we ...Investigation of patient-derived primary tissues is of great importance in the biomedical field,but recent tissue slicing and cultivation techniques still have difficulties in satisfying clinical requirements.Here,we propose a controllable histotomy strategy that utilizes hierarchical magnetic microneedle array robots to tailor primary tissues and establish the desired high-throughput tissue-on-a-chip.This histotomy is performed using a three-dimensional printed,mortise-tenon-structured slicing device coupled with a magnetic-particle-loaded and pagoda-shaped microneedle array scaffold.Due to the multilayered struc-ture of these microneedles,tissue specimens can be fixed onto the microneedle scaffold via mechanical interlocking,thereby effectively avoiding tissue slipping during the slicing process.Owing to the encapsu-lation of magnetic microneedle fragments,these tissue pieces can act as magnetically responsive biohybrid microrobots and can be easily manipulated by magnetic fields,facilitating their separation,transportation,and dynamic culture.Using this strategy,we demonstrate that primary pancreatic cancer tissues can be tailored into tiny pieces and cultured in multilayered microfluidic chips for efficient high-throughput drug screening,indicating the promising future of this technique’s application in clinical settings.展开更多
Lidocaine hydrochloride(LIDH) as an anesthetic is widely used in local anesthesia. Dissolving microneedles(MNs) have great application value in the field of skin anesthesia. However, the limited drug-loading of dissol...Lidocaine hydrochloride(LIDH) as an anesthetic is widely used in local anesthesia. Dissolving microneedles(MNs) have great application value in the field of skin anesthesia. However, the limited drug-loading of dissolving MNs is an existing challenge that affects clinical use. In this study, we have screened isomaltulose(ISO) as the proper matrix material for the MNs by using molecular dynamics(MD) simulation. Our findings indicate that ISO has good compatibility with LIDH, and the LIDH-loaded ISO MNs(LI-MNs) have high drug-loading capacity. The drug-loading capacity of LI-MNs could reach 80%, and it could effectively puncture the skin. In addition, the preparation method of customized LI-MNs was established based on three-dimensional(3D) printing technology. It was shown that the administration time of LI-MNs could be controlled within 3 min. Also, the LI-MNs were able to provide the local anesthetic efficacy within2 min and sustained for more than 2 h. Significantly, LI-MNs had more efficient drug efficacy compared to the topical creams and the majority of existing LIDH-loaded dissolving MNs. They even provided a longer duration of action than the injections. Overall, the LI-MNs with high drug-loading have a promising application prospect.展开更多
Therapeutic cancer vaccines have undergone a resurgence in the past decade.Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis,percutaneous vaccination is consid...Therapeutic cancer vaccines have undergone a resurgence in the past decade.Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis,percutaneous vaccination is considered to be an ideal treatment route.For convenient administration,the recent development of microneedles(MNs)provides a safe,painless,and low-cost transdermal delivery strategy,which could bypass the first-pass metabolism of vaccines for enhanced stability and bioavailability.However,the therapeutic effect of MNs-based cancer vaccines is not optimal,which is limited by the complex set of host,tumor,and environmental factors,as well as the limited vaccine loading capacity.Therefore,further improvements are still required to push their clinical translation.In this critical review,we deliberate on how to improve the therapeutic effect of MNs-based vaccines for cancer immunotherapy,summarize the recent advances in MNs-based cancer vaccination,and provide an overview of various design strategies and mechanisms for active or passive targeting delivery,aiming to develop safer,more effective,and more stable MNs-based cancer vaccines.Finally,we briefly describe the potential of vaccine platforms in combination with other therapies,suggest the need to design vaccines according to specific circumstances,and discuss the biosafety of repeated administration for enhancing clinical efficacy.展开更多
The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional...The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.展开更多
基金supported through grants from the Key Fields of Biomedicine and Health Foundation of Colleges and Universities in Guangdong Province(2022ZDZX2017)the National Natural Science Foundation of China(82104354)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(2022A1515012154)the funding grants from University of Macao and the University of Macao Development Foundation(MYRG2023-GRG00184-ICMS-UMDF and MYRG2024-GRG00271-ICMS-UMDF).
文摘The use of microneedles(MNs)has been established as an effective transdermal drug delivery strategy that has been extensively deployed for treating various diseases,including skin diseases.MNs can surpass the constraints of conventional drug delivery methods by their superior safety and efficacy through precise targeting,while simultaneously enabling painless delivery.Currently,MNs are increasingly used as carriers for drug delivery,with the loading of insoluble drugs to improve their treatment efficiency or combining with bioactive substances for the construction of an efficient drug delivery system to maximize the effects of bioactive substances.The methods used for preparation MNs are diverse,enabling them to meet the requirements of most applications.The emergence of MNs has addressed the shortcomings associated with insoluble drugs,expanded the applications of bioactive substances,and improved their use in clinical practice.This review summarizes current information on the application of MNs in a variety of skin diseases,such as psoriasis,vitiligo,alopecia,hypertrophic scarring,atopic dermatitis,melanoma,acne,and skin infections.The current clinical applications and future opportunities for MNs in the treatment of skin diseases are also discussed.Despite substantial progress in the clinical application of MNs as delivery vectors,issues such as low drug loading and poor mechanical strength during MNs preparation remain the main challenges.Therefore,clinical implementation of MNs-based therapies remains limited,highlighting key opportunities for future research.
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.
基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSIT)(No.RS-2023-00256265,RS-2024-00352352,RS-2024-00405818)the Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korea government(the Ministry of Science and ICT,the Ministry of Health&Welfare).(No.25A0102L1)support from the Market-led K-sensor technology program(RS-2022-00154781,Development of large-area wafer-level flexible/stretchable hybrid sensor platform technology for form factor-free highly integrated convergence sensor),funded By the Ministry of Trade,Industry&Energy(MOTIE,Korea).
文摘Microneedles(MNs)have been extensively investigated for transdermal delivery of large-sized drugs,including proteins,nucleic acids,and even extracellular vesicles(EVs).However,for their sufficient skin penetration,conventional MNs employ long needles(≥600μm),leading to pain and skin irritation.Moreover,it is critical to stably apply MNs against complex skin surfaces for uniform nanoscale drug delivery.Herein,a dually amplified transdermal patch(MN@EV/SC)is developed as the stem cell-derived EV delivery platform by hierarchically integrating an octopusinspired suction cup(SC)with short MNs(≤300μm).While leveraging the suction effect to induce nanoscale deformation of the stratum corneum,MN@EV/SC minimizes skin damage and enhances the adhesion of MNs,allowing EV to penetrate deeper into the dermis.When MNs of various lengths are applied to mouse skin,the short MNs can elicit comparable corticosterone release to chemical adhesives,whereas long MNs induce a prompt stress response.MN@EV/SC can achieve a remarkable penetration depth(290μm)for EV,compared to that of MN alone(111μm).Consequently,MN@EV/SC facilitates the revitalization of fibroblasts and enhances collagen synthesis in middle-aged mice.Overall,MN@EV/SC exhibits the potential for skin regeneration by modulating the dermal microenvironment and ensuring patient comfort.
基金supported by the National Natural Science Foundation of China(82274225)NATCM's Project of High-level Construction of Key TCM Disciplines-Beijing University of Chinese Medicine-Life Science from the Perspective of Chinese Medicine(zyyzdxk-2023263).
文摘Objective:To assess the efficiency of a Sophora flavescens Ait(S.flavescens,Ku Shen)-soluble microneedle(SFA-MN)for improving skin lesion symptoms in mice with psoriasis.Methods:SFA-MNs were prepared using a two-mold molding process with 20%w/v poly-vinylpyrrolidone and 15%w/v polyvinyl alcohol.The SFA-MNs were assessed for morphology,mechanical properties,in vitro dissolution,identification of components,and skin lesion improvement in imiquimod-induced psoriasis mice.Results:The SFA-MNs demonstrated good mechanical properties for efficiently penetrating the dermis,facilitating efficient drug delivery.Furthermore,they effectively inhibited mast cell levels in the dorsal lesion area of psoriasis mice and reduced the expression of the T-lymphocyte factor cluster of differ-entiation 3 and tumor necrosis factor-a.In addition,this system alleviated skin inflammation,splenic swelling,and thymic atrophy in the psoriasis-like mouse model.Seven major components were detected from SFA-MNs by comparison of the mass-to-nucleus ratios(m/z)of the secondary fragments N-methylcytisine,5a,9a-dihydroxymatrine,sophoramine,matrine,oxysophocarpine,oxymatrine,and kushenol O.Conclusion:The drug delivery strategy combining traditional herbal S.flavescens with soluble micro-needle technology provides more targeted and effective immune regulation for treating psoriasis-like mice models,enabling enhanced therapeutic effects compared with the control group.
基金financially supported by the National Natural Science Foun-dation of China(22278257)the Key R&D Program of Shaanxi Province(2024SF-YBXM-586)the Project of Innovation Capability Support Program in Shaanxi Province(2024ZC-KJXX-005)。
文摘Rapidly-advancing microneedle-based bioelectronics integrated with electrical stimulation(ES)therapy exhibit significant potential for improving chronic wound management.Herein,bio-inspired by the serrated structure of bee-stingers,we developed a temperature-sensitive,two-stage microneedle-based electro active platform(GP-PPy/PLA-MN)featuring rivet-like micros tructures that integrates intelligent,precise drug-releasing,ES-transmission,and real-time wound-assessment monitoring for comprehensive chronic wound-management and diagnostic therapy.The bionic-design mechanically anchors the microneedle beneath the skin's dermis,while GP-PPy/PLA-MN demonstrates versatile therapeutic characteristics,including outstanding biocompatibility,antimicrobial properties,and antimigratory origins.The GP-PPy/PLA-MN enables the sustained release of insulin at body temperature for up to24 hours through the poly-N-isopropyl acrylamide grafted amidated-gelatin-based thermo-sensitive hydrogel at the needle-tip,thereby providing long-term stable blood glucose control.GP-PPy/PLA-MN indicates its potential as a novel bioelectronics-based patch to record the temperature and humidity during the wound-healing process,realizing significant wound diagnosis and real-time wound assessment,and fundamentally facilitating the therapeutic efficacy by supplying solid data to protect the clinical practice.Extensive in vitro and in vivo studies have demonstrated that GP-PPy/PLA-MN can provide effective ES and sustained drug release,thereby promoting chronic wound healing and increasing the wound healing rate by 20%compared to the control group after 14 days of treatment.This innovative approach combines bioelectronics with intelligent drug delivery and microneedling technology to effectively address the critical challenges of chronic wound management,offering promising prospects for precision diagnostics and therapeutic interventions.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82204340,82173954,and 82073815)the Natural Science Foundation of Jiangsu Province,China(Grant No.:BK20221048)+1 种基金the Jiangsu Funding Program for Excellent Postdoctoral Talent,China(Grant No.:2022ZB295)Key Laboratory Project of Quality Control of Chinese Herbal Medicines and Decoction Pieces,Gansu Institute for Drug Control,China(Grant No.:2024GSMPA-KL02).
文摘Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin interstitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50%.In the concentration range of 1×10_(7) to 1×10^(10) colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87%.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.
基金supported by China Postdoctoral Science Foundation(2023M740789)Guangdong Basic and Applied Basic Research Foundation(2023A1515110441,2024A1515011248,2024A1515030104)+1 种基金Guangzhou S&T Programme Foundation(202206010051,202205110009)Young Talent Support Project of Guangzhou Association for S&T(QT20220101041).
文摘Nanoparticles-incorporated hydrogel microneedles(NPs-HMN)have attracted significant attention due to their exceptional biomedical applications.The arrayed needle tips of NPsHMN effectively penetrate the skin or tissue,enabling minimally invasive and painless delivery of therapeutic molecules into the tissue microenvironment.This approach has shown significant improvements in bioavailability and patient compliance.Moreover,the functionalized hydrogel materials of NPs-HMN exhibit a three-dimensional network structure resembling the extracellular matrix,along with controllable drug release,exceptional swelling ability,hydrophilicity,and biocompatibility.These characteristics broaden the potential applications of HMN in therapeutic and biosensing contexts.In addition,the incorporation of nanoparticles(NPs)has been shown to improve the solubility of hydrophobic drugs,enhance mechanical properties,enable intelligent drug release,and facilitate precise targeting of HMN.The versatility and diversity of treatment options afforded by NPs-HMN contribute to significant advancements in animal models and clinical settings,as well as offer valuable insights for biomaterial development.This review provides a comprehensive examination of the fabrication strategies of NPs-HMN and their recent advancements in biomedical applications.We also analyze the mechanisms,advantages,challenges,and future prospects of this system in enhancing drug delivery efficiency to provide theoretical references for further breakthroughs in novel delivery platforms.
基金Supported by Guangdong Provincial Key-Area Research and Development Program(Grant No.2023B0101200014)Guangdong Provincial Natural Science Foundation(Grant No.2024A1515010440).
文摘Microneedle(MN)is a medical device containing an array of needles with a micrometer-scale.It can penetrate the human stratum corneum painlessly and efficiently for treatment and diagnosis purposes.Currently,the materials commonly used to manufacture MNs include silicon,polymers,ceramics and metals.Metallic MNs(MMNs)have drawn significant attention owing to its superior mechanical properties,machinability,and biocompatibility.This paper is a state-of-the-art review of the structure,fabrication technologies,and applications of MMNs.According to the relative position of the axis of MN and the plane of the substrate,MMNs can be divided into in-plane and out-of-plane.Solid,hollow,coated and porous MMNs are also employed to characterize their internal and surface structures.Until now,numerous fabrication technologies,including cutting tool machining,non-traditional machining,etching,hot-forming,and additive manufacturing,have been used to fabricate MMNs.The recent advances in the application of MMNs in drug delivery,disease diagnosis,and cosmetology are also discussed in-depth.Finally,the shortcomings in the fabrication and application of MMNs and future directions for development are highlighted.
文摘Objective:Microneedles(MNs),as a key component of third-generation transdermal drug delivery sys-tems,show strong potential for obesity treatment.This study aimed to integrate traditional Chinese medicine(TCM)therapies,including Chinese patent medicine(CPM)injections and patches,with MN technology to identify commonly used administration sites and Chinese medicinal material(CMM)con-stituents suitable for MN-based weight loss interventions.Methods:Literature was retrieved from PubMed,Web of Science,Google Scholar,CNKI,and Google Patents.First,existing studies on MN-based weight loss were narratively reviewed.Then,studies on CPM injections or patches were analyzed to extract intervention elements,including administration sites,CMM constituents,and symptoms.Acupoint-symptom and CMM constituent-symptom pairs were compiled,and key nodes were identified through complex network analysis using eigenvector centrality,PageRank,and betweenness centrality.Results:Forty-four studies and thirteen patents were included.The review indicated that MN-based in-terventions demonstrated significant weight loss effects;however,current research remains limited by a focus on fat-deposition sites and insufficient development of CMM carriers.Network analysis identi-fied Guanyuan(CV4)and Poria cocos(Fuling)as central nodes across all metrics,suggesting their strong potential as key elements in MN-based therapies.Conclusion:CV4 and Poria cocos represent promising candidates for delivery sites and CMM constituents in MN-mediated obesity treatment.By integrating TCM principles with modern MN technology,these findings provide a theoretical basis for developing more targeted,efficient,and integrative anti-obesity interventions.
基金supported by Shandong Provincial Natural Science Foundation Innovation and Development Joint Project,China(Grant No.:ZR2021LZY039)Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan,China(Grant No.:2021ZB184)。
文摘Microneedles(MNs)have attracted increasing attention as a transdermal delivery system(TDDS)[1].However,traditional volatile Chinese medicines cannot be dissolved in conventional soluble MN materials,such as hyaluronic acid and chitosan,making it difficult for many traditional Chinese medicine ingredients to be applied to MN.Elemene(ELE)was successfully isolated from Curcuma longa,and has numerous antitumor and curative effects[2].
基金financial support from the Beijing Natural Science Foundation(No.L234020)the National Natural Science Foundation of China(Nos.12472325 and 12272032)the 111 Project(No.B13003).
文摘Microneedles(MNs)are an innovative and viable option for drug delivery that offer the distinct advantages of minimal invasiveness,painlessness,stable drug loading,efficient drug permeation,and biocompatibility.MNs were first used to penetrate the skin surface and facilitate transcutaneous drug delivery with great success.Recent applications of MNs have extended to non-transdermal drug delivery,specifically,to various tissues and organs.This review captures the fabrication methods for MNs,discusses advanced design strategies for achieving controlled drug release,and summarizes current MN applications in delivering multiple therapeutic agents to the cardiovascular,digestive(e.g.,oral cavity),reproductive,and central nervous systems.The findings in this review would contribute toward the improved designs of MN systems that can be modified according to purpose,including material selection,structural design,choice of fabrication methods,and tissue considerations,to determine the optimal therapeutic regimen for the target treatment area.
基金supported by the Joint Funds of National Natural Science Foundation of China(No.U22A20162)the Natural Science Foundation of Hebei Province of China(No.C2021202002)+1 种基金the National Natural Science Foundation of China(No.52271245),the Natural Science Foundation of Tianjin(No.21JCQNJC01280)the financial support from the Danish Council for Independent Research(9040-00219B),European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement ENSIGN(Project ID:101086226),L4DNANO(Project ID:101086227).
文摘Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.
基金supported by the Beijing Natural Science Foundation(Nos.7252285 and L246001)the National Natural Science Foundation of China(Nos.U21A20394 and 52305314)the National Key Research and Development Program of China(No.2023YFB4605800).
文摘Myocardial infarction(MI)is a challenging condition that results in scar formation on the ventricular wall,causing myocardial damage and ventricular thinning.Engineered cardiac patches(ECPs)designed to regenerate myocardial tissue have been proposed to repair the ventricular wall and replenish myocardial cells.However,their clinical use is limited by manufacturing and fixation challenges.This study introduces a manufacturing strategy for a composite ECP,which comprises an antiadhesion shell layer,a conductive myocardial tissue,and an exosome-laden microneedle substrate.The ECP can anchor to the infarcted myocardium through its microneedle substrate.Meanwhile,its outer shell prevents nonspecific adhesion,enabling stable and suture-free attachment.Using this microneedle substrate,we applied a 3D-printed ECP in a rat model of post-MI repair.Our results showed that this strategy reduced left ventricular damage,improved cardiac ejection fraction,decreased the fibrotic area,increased ventricular wall thickness,improved microvascular recovery,and thus facilitated the repair of maladaptive ventricular remodeling post-MI.This microneedle substrate holds great promise for use in the fixation of patches during the repair of myocardial tissue and other organs,thereby promoting the clinical application of tissue-engineered patches.
基金support from the National Natural Science Foundation of China(No.82472444).
文摘Chronic diabetic wounds result from a disrupted microenvironment where oxidative stress,impaired angiogenesis,and persistent infection create a vicious cycle that delays healing.Unfortunately,existing treatments often fail to address these interrelated issues,resulting in suboptimal healing.Here,we propose a base-tip dual-component hydrogel microneedle(MN)system(GBEVs-pVEGF/AgNPs@MNs),consisting of a tip loaded with plant-bacterial hybrid extracellular vesicles(GBEVs-pVEGF)and a base containing silver nanoparticles(AgNPs).Upon penetrating the necrotic tissue of diabetic wounds,our multifunctional MNs could effectively deliver GBEVs-pVEGF,thereby alleviating oxidative stress,promoting cell migration,and facilitating angiogenesis.Additionally,the physical barrier formed by the basal layer synergistically mitigates persistent bacterial infections during wound healing in conjunction with the antimicrobial agent AgNPs.This multifunctional MN system,integrating antioxidant,angiogenic,and antimicrobial properties,effectively restores the disrupted wound microenvironment,offering significant potential for accelerating diabetic wound healing.
基金supported by the National Natural Science Foundation of China(No.31971271)The Natural Science Foundation of Fujian Province of China(No.2022J01794)The Science and Technology Plan Project of Quanzhou(No.2021N033S).
文摘Delayed or non-healing of diabetic wounds is a significant complication,often attributed to high glucose-induced M1 macrophage accumulation,impaired angiogenesis,and reactive oxygen species(ROS)buildup.Addressing this,we introduced a strontium polyphenol network microneedle patch(SrC-MPNs@MN-PP)for percutaneous drug delivery.This patch,formulated with polymer poly(γ-glutamic acid)(γ-PGA)and epsilon-poly-l-lysine(ε-PLL),incorporates strontium polyphenol networks(SrC-MPNs).The release of chlorogenic acid(CGA)from SrC-MPNs not only neutralizes ROS,but strontium ions also foster angiogen-esis.Consequently,SrC-MPNs@MN-PP can ameliorate the diabetic wound microenvironment and expedite healing.
基金supported in part by the National Natural Science Foundation of China(Grant No.62104056)the Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ21F010010)+4 种基金the National Natural Science Foundation of China(Grant Nos.62141409 and 62204204)the National Key R&D Program of China(Grant No.2022ZD0208602)the Zhejiang Provincial Key Research&Development Fund(Grant Nos.2019C04003 and 2021C01041)the Shanghai Sailing Program(Grant No.21YF1451000)the Key Research and Development Program of Shaanxi(Grant No.2022GY-001).
文摘Flexible pressure sensors have many potential applications in the monitoring of physiological signals because of their good biocompatibil-ity and wearability.However,their relatively low sensitivity,linearity,and stability have hindered their large-scale commercial application.Herein,aflexible capacitive pressure sensor based on an interdigital electrode structure with two porous microneedle arrays(MNAs)is pro-posed.The porous substrate that constitutes the MNA is a mixed product of polydimethylsiloxane and NaHCO3.Due to its porous and interdigital structure,the maximum sensitivity(0.07 kPa-1)of a porous MNA-based pressure sensor was found to be seven times higher than that of an imporous MNA pressure sensor,and it was much greater than that of aflat pressure sensor without a porous MNA structure.Finite-element analysis showed that the interdigital MNA structure can greatly increase the strain and improve the sensitivity of the sen-sor.In addition,the porous MNA-based pressure sensor was found to have good stability over 1500 loading cycles as a result of its bilayer parylene-enhanced conductive electrode structure.Most importantly,it was found that the sensor could accurately monitor the motion of afinger,wrist joint,arm,face,abdomen,eye,and Adam’s apple.Furthermore,preliminary semantic recognition was achieved by monitoring the movement of the Adam’s apple.Finally,multiple pressure sensors were integrated into a 33 array to detect a spatial pressure distribu-×tion.Compared to the sensors reported in previous works,the interdigital electrode structure presented in this work improves sensitivity and stability by modifying the electrode layer rather than the dielectric layer.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(T2225003,52073060,61927805)+2 种基金the Nanjing Medical Science and Technique Development Foundation(ZKX21019)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)the Guangdong Basic and Applied Basic Research Foundation(2021B1515120054).
文摘Investigation of patient-derived primary tissues is of great importance in the biomedical field,but recent tissue slicing and cultivation techniques still have difficulties in satisfying clinical requirements.Here,we propose a controllable histotomy strategy that utilizes hierarchical magnetic microneedle array robots to tailor primary tissues and establish the desired high-throughput tissue-on-a-chip.This histotomy is performed using a three-dimensional printed,mortise-tenon-structured slicing device coupled with a magnetic-particle-loaded and pagoda-shaped microneedle array scaffold.Due to the multilayered struc-ture of these microneedles,tissue specimens can be fixed onto the microneedle scaffold via mechanical interlocking,thereby effectively avoiding tissue slipping during the slicing process.Owing to the encapsu-lation of magnetic microneedle fragments,these tissue pieces can act as magnetically responsive biohybrid microrobots and can be easily manipulated by magnetic fields,facilitating their separation,transportation,and dynamic culture.Using this strategy,we demonstrate that primary pancreatic cancer tissues can be tailored into tiny pieces and cultured in multilayered microfluidic chips for efficient high-throughput drug screening,indicating the promising future of this technique’s application in clinical settings.
基金supported by the National Key Research and Development Program of China (No.2021YFF1200800)the Sichuan Science and Technology Program (Nos.2021JDTD0001,2022YFQ0004)the Natural Science Foundation of Sichuan Province (No.2023NSFSC1629)。
文摘Lidocaine hydrochloride(LIDH) as an anesthetic is widely used in local anesthesia. Dissolving microneedles(MNs) have great application value in the field of skin anesthesia. However, the limited drug-loading of dissolving MNs is an existing challenge that affects clinical use. In this study, we have screened isomaltulose(ISO) as the proper matrix material for the MNs by using molecular dynamics(MD) simulation. Our findings indicate that ISO has good compatibility with LIDH, and the LIDH-loaded ISO MNs(LI-MNs) have high drug-loading capacity. The drug-loading capacity of LI-MNs could reach 80%, and it could effectively puncture the skin. In addition, the preparation method of customized LI-MNs was established based on three-dimensional(3D) printing technology. It was shown that the administration time of LI-MNs could be controlled within 3 min. Also, the LI-MNs were able to provide the local anesthetic efficacy within2 min and sustained for more than 2 h. Significantly, LI-MNs had more efficient drug efficacy compared to the topical creams and the majority of existing LIDH-loaded dissolving MNs. They even provided a longer duration of action than the injections. Overall, the LI-MNs with high drug-loading have a promising application prospect.
基金supported by the National Natural Science Foundation of China(No.82073799)the Natural Science Foundation of Hunan Province in China(No.2021JJ20084)the Science and Technology Innovation Program of Hunan Province(No.2021RC3020)。
文摘Therapeutic cancer vaccines have undergone a resurgence in the past decade.Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis,percutaneous vaccination is considered to be an ideal treatment route.For convenient administration,the recent development of microneedles(MNs)provides a safe,painless,and low-cost transdermal delivery strategy,which could bypass the first-pass metabolism of vaccines for enhanced stability and bioavailability.However,the therapeutic effect of MNs-based cancer vaccines is not optimal,which is limited by the complex set of host,tumor,and environmental factors,as well as the limited vaccine loading capacity.Therefore,further improvements are still required to push their clinical translation.In this critical review,we deliberate on how to improve the therapeutic effect of MNs-based vaccines for cancer immunotherapy,summarize the recent advances in MNs-based cancer vaccination,and provide an overview of various design strategies and mechanisms for active or passive targeting delivery,aiming to develop safer,more effective,and more stable MNs-based cancer vaccines.Finally,we briefly describe the potential of vaccine platforms in combination with other therapies,suggest the need to design vaccines according to specific circumstances,and discuss the biosafety of repeated administration for enhancing clinical efficacy.
基金supported by the National Natural Science Foundation of China(82371032,82070923)the Major Basic Research Project of the Natural Science Foundation of Shandong Province(ZR2023ZD60)+1 种基金the Taishan Scholar Program(20231255)the Academic Promotion Program of Shandong First Medical University(2019RC009).
文摘The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.
