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
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
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
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
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
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
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
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
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
To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a...To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a kind of particles by a reversible addition-fragmentation chain transfer(RAFT)method containing a phenylboronic acid group as the sensor of glucose and carrier of insulin.poly(ethylene glycol)(PEG)-2-(dodecylthio(thiocarbonyl)thio)-2-methylpropionic acid(DDMAT)was synthesized as a macromolecular RAFT agent,which was then reacted with 3-acrylamidophenylboronic acid(AAPBA)to synthesize the block copolymer PEG-b-PAAPBA.Glucose-responsive particles loaded with insulin were prepared by self-assembly based on hydrophilic-hydrophobic interactions.Microneedle patches loaded with glucose-responsive particles were prepared using hyaluronic acid as the substrate.The insulin release behavior of the particles in glucose solutions of 0,100,and 400 mg/dL showed significant glucose responsiveness and good biosafety.The results of blood glucose control experiments in rats indicate that a single microneedle patch can effectively maintain normal blood glucose for over 7 h.展开更多
Objective:To determine the main components of Astragalus membranaceus(Fisch.)Bge(A.membranaceus,Huang Qi),Astragaloside IV(AIV)and Astragalus polysaccharides(AP),to characterize their properties,evaluate their in vivo...Objective:To determine the main components of Astragalus membranaceus(Fisch.)Bge(A.membranaceus,Huang Qi),Astragaloside IV(AIV)and Astragalus polysaccharides(AP),to characterize their properties,evaluate their in vivo efficacy,and to analyze drug diffusion using dissolving microneedle(DMN)technology in vivo.Methods: Respectively,AIV-and AP-loaded DMNs comprising chitosan(CTS)and polyvinyl alcohol(PVA)were prepared via dual-mold forming.Their morphology,mechanical properties,in vivo solubility,and skin irritation characteristics were tested.In vivo efficacy was assessed in cyclophosphamide-induced immunosuppressed mice,in vivo diffusion of AIV and AP by DMNs and conventional methods was compared,and the rheological properties of AIV-CTS-PVA and AP-CTS-PVA mixtures were measured.Results: Subcutaneous dissolution and absorption of AIV-CTS-PVA and AP-CTS-PVA microneedles(MNs)at low doses(50%–17%of intraperitoneal AIV injection and 12%–4%of intravenous AP injection)reduced the spleen index and acid phosphatase activity in immunosuppressed mouse models,increased the thymus index,and achieved equivalent or better systemic therapeutic effects.Compared with injections,AIV and AP achieved controllable solid-liquid conversion through delivery with CTS-PVA MNs,resulting in highly localized aggregation within 48 h,reducing the initial explosive effect of the drug,and achieving stable and slow drug release.Conclusion: The present study enhances our understanding of the efficacy and remote effects of drug-loaded DMNs from a traditional Chinese medicine(TCM)perspective,thereby promoting the development of precise and efficient delivery of TCM and further expanding the drug-loading range and application scenarios for DMNs.展开更多
Objective:We have developed a baroreceptor-inspired microneedle skin patch for pressure-controlled drug release.Impact Statement:This design is inspired by the skin baroreceptors,which are mechanosensitive elements of...Objective:We have developed a baroreceptor-inspired microneedle skin patch for pressure-controlled drug release.Impact Statement:This design is inspired by the skin baroreceptors,which are mechanosensitive elements of the peripheral nervous system.We adopt the finger touching to trigger the electric stimulation,ensuring a fast-response and user-friendly administration with potentially minimal off-target effects.Introduction:Chronic skin diseases bring about large,recurrent skin damage and often require convenient and timely transdermal treatment.Traditional methods lack spatiotemporal controllable dosage,leaving a risk of skin irritation or drug resistance issues.Methods:The patch consists of drug-containing microneedles and stretchable electrode array.The electrode array,integrated with the piezoconductive switch and flexible battery,provides a mild electric current only at the spot that is pressed.Drugs in microneedles will then flow along the current into the skin tissues.The stretchable feature also provides the mechanical robustness and electric stability of the device on large skin area.Results:This device delivers Cy3 dye in pig skin with spatiotemporally controlled dosage,showing~8 times higher fluorescence intensity than the passive delivery.We also deliver insulin and observe the reduction of the blood glucose level in the mouse model upon pressing.Compared with passive delivery without pressing,the dosage of drugs released by the simulation is 2.83 times higher.Conclusion:This baroreceptor-inspired microneedle skin patch acts as a good example of the biomimicking microneedle device in the precise control of the drug release profile at the spatiotemporal resolution.展开更多
Transdermal microneedle(MN)patches are a promising tool used to transport a wide variety of active compounds into the skin.To serve as a substitute for common hypodermic needles,MNs must pierce the human stratum corne...Transdermal microneedle(MN)patches are a promising tool used to transport a wide variety of active compounds into the skin.To serve as a substitute for common hypodermic needles,MNs must pierce the human stratum corneum(~10 to 20μm),without rupturing or bending during penetration.This ensures that the cargo is released at the predetermined place and time.Therefore,the ability of MN patches to sufficiently pierce the skin is a crucial requirement.In the current review,the pain signal and its management during application of MNs and typical hypodermic needles are presented and compared.This is followed by a discussion on mechanical analysis and skin models used for insertion tests before application to clinical practice.Factors that affect insertion(e.g.,geometry,material composition and cross-linking of MNs),along with recent advancements in developed strategies(e.g.,insertion responsive patches and 3D printed biomimetic MNs using two-photon lithography)to improve the skin penetration are highlighted to provide a backdrop for future research.展开更多
Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work r...Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.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 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 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.
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 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 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 (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.
基金supported by the Natural Science Foundation of Zhejiang Province(No.LHDMZ22H300003)the Science and Technology Program of Zhejiang Province(No.2019C03063),China。
文摘To overcome the pain and risk of hypoglycemia in insulin administration,glucose-responsive microneedles have been developed by researchers,which could release insulin according to the blood glucose level.We designed a kind of particles by a reversible addition-fragmentation chain transfer(RAFT)method containing a phenylboronic acid group as the sensor of glucose and carrier of insulin.poly(ethylene glycol)(PEG)-2-(dodecylthio(thiocarbonyl)thio)-2-methylpropionic acid(DDMAT)was synthesized as a macromolecular RAFT agent,which was then reacted with 3-acrylamidophenylboronic acid(AAPBA)to synthesize the block copolymer PEG-b-PAAPBA.Glucose-responsive particles loaded with insulin were prepared by self-assembly based on hydrophilic-hydrophobic interactions.Microneedle patches loaded with glucose-responsive particles were prepared using hyaluronic acid as the substrate.The insulin release behavior of the particles in glucose solutions of 0,100,and 400 mg/dL showed significant glucose responsiveness and good biosafety.The results of blood glucose control experiments in rats indicate that a single microneedle patch can effectively maintain normal blood glucose for over 7 h.
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 determine the main components of Astragalus membranaceus(Fisch.)Bge(A.membranaceus,Huang Qi),Astragaloside IV(AIV)and Astragalus polysaccharides(AP),to characterize their properties,evaluate their in vivo efficacy,and to analyze drug diffusion using dissolving microneedle(DMN)technology in vivo.Methods: Respectively,AIV-and AP-loaded DMNs comprising chitosan(CTS)and polyvinyl alcohol(PVA)were prepared via dual-mold forming.Their morphology,mechanical properties,in vivo solubility,and skin irritation characteristics were tested.In vivo efficacy was assessed in cyclophosphamide-induced immunosuppressed mice,in vivo diffusion of AIV and AP by DMNs and conventional methods was compared,and the rheological properties of AIV-CTS-PVA and AP-CTS-PVA mixtures were measured.Results: Subcutaneous dissolution and absorption of AIV-CTS-PVA and AP-CTS-PVA microneedles(MNs)at low doses(50%–17%of intraperitoneal AIV injection and 12%–4%of intravenous AP injection)reduced the spleen index and acid phosphatase activity in immunosuppressed mouse models,increased the thymus index,and achieved equivalent or better systemic therapeutic effects.Compared with injections,AIV and AP achieved controllable solid-liquid conversion through delivery with CTS-PVA MNs,resulting in highly localized aggregation within 48 h,reducing the initial explosive effect of the drug,and achieving stable and slow drug release.Conclusion: The present study enhances our understanding of the efficacy and remote effects of drug-loaded DMNs from a traditional Chinese medicine(TCM)perspective,thereby promoting the development of precise and efficient delivery of TCM and further expanding the drug-loading range and application scenarios for DMNs.
基金support by General Research Fund(GRF)grant from the Research Grants Council(RGC)of the Hong Kong Special Administrative Region China(CityU11200820,CityU11100323)the Mainland/Hong Kong Joint Research Scheme sponsored by the RGC Hong Kong and the National Natural Science Foundation of China(N_CityU118/20).
文摘Objective:We have developed a baroreceptor-inspired microneedle skin patch for pressure-controlled drug release.Impact Statement:This design is inspired by the skin baroreceptors,which are mechanosensitive elements of the peripheral nervous system.We adopt the finger touching to trigger the electric stimulation,ensuring a fast-response and user-friendly administration with potentially minimal off-target effects.Introduction:Chronic skin diseases bring about large,recurrent skin damage and often require convenient and timely transdermal treatment.Traditional methods lack spatiotemporal controllable dosage,leaving a risk of skin irritation or drug resistance issues.Methods:The patch consists of drug-containing microneedles and stretchable electrode array.The electrode array,integrated with the piezoconductive switch and flexible battery,provides a mild electric current only at the spot that is pressed.Drugs in microneedles will then flow along the current into the skin tissues.The stretchable feature also provides the mechanical robustness and electric stability of the device on large skin area.Results:This device delivers Cy3 dye in pig skin with spatiotemporally controlled dosage,showing~8 times higher fluorescence intensity than the passive delivery.We also deliver insulin and observe the reduction of the blood glucose level in the mouse model upon pressing.Compared with passive delivery without pressing,the dosage of drugs released by the simulation is 2.83 times higher.Conclusion:This baroreceptor-inspired microneedle skin patch acts as a good example of the biomimicking microneedle device in the precise control of the drug release profile at the spatiotemporal resolution.
基金the European Horizon 2020 Research and Innovation Programme under Grant Agreement No.899349(5D NanoPrinting).
文摘Transdermal microneedle(MN)patches are a promising tool used to transport a wide variety of active compounds into the skin.To serve as a substitute for common hypodermic needles,MNs must pierce the human stratum corneum(~10 to 20μm),without rupturing or bending during penetration.This ensures that the cargo is released at the predetermined place and time.Therefore,the ability of MN patches to sufficiently pierce the skin is a crucial requirement.In the current review,the pain signal and its management during application of MNs and typical hypodermic needles are presented and compared.This is followed by a discussion on mechanical analysis and skin models used for insertion tests before application to clinical practice.Factors that affect insertion(e.g.,geometry,material composition and cross-linking of MNs),along with recent advancements in developed strategies(e.g.,insertion responsive patches and 3D printed biomimetic MNs using two-photon lithography)to improve the skin penetration are highlighted to provide a backdrop for future research.
基金the National Natural Science Foundation of China(Nos.62003023,32071407,52073138,52003018 and 52003019)Beijing Natural Science Foundation(No.7212204)Beijing Advanced Innovation Center for Biomedical Engineering and Beihang University.
文摘Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.
