Background and Objectives:Microneedling has been introduced as a new technique to address the growing concern of facial skin photoaging.Kangfuxin liquid has been found to promote the process of skin wound repair,inclu...Background and Objectives:Microneedling has been introduced as a new technique to address the growing concern of facial skin photoaging.Kangfuxin liquid has been found to promote the process of skin wound repair,including reducing inflammatory response,improving immunity and enhancing antioxidant levels.In this prospective randomized double-blinded study,we wanted to explore the clinical efficacy and safety of Kangfuxin liquid combined with microneedling in treating facial skin photoaging.Methods:57 patients with facial skin photoaging were randomly divided into two groups.The treatment group(28 cases)received microneedle therapy with Kangfuxin liquid,while the control group(29 cases)received microneedle therapy with physiological saline.The treatment interval was 4 weeks,and a total of 3 treatments were performed.Compare the VISIA scores of facial photoaging features such as wrinkles,texture,pores,spots and ultraviolet pigmentation between two groups of patients before and after treatment,Global Score for Photoaging,satisfaction evaluation,and record the occurrence of adverse reactions.Results:After treatment,the treatment group showed more significant improvement in wrinkles,texture,pores,spots and ultraviolet pigmentation,and the Global Score for Photoaging was better than the control group(P<0.05).The satisfaction rate with improving skin in the treatment group was 85.71%,which was higher than 75.86%in the control group(P<0.05).Both groups did not experience adverse reactions such as skin infection,pigmentation or hypopigmentation,scar formation,or worsening of melasma.Conclusion:Kangfuxin liquid combined with microneedling therapy has a good improvement effect on facial skin photoaging,with a low incidence of adverse reactions and high patient satisfaction.It is worthy of clinical promotion.展开更多
Objective:To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel.Methods:In this study,the sodium urate and LPS were used on rats and ...Objective:To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel.Methods:In this study,the sodium urate and LPS were used on rats and mice to construct the model.Bee venom gelemicroneedle combination effect on the model is to determine the role of microneedle gel permeation by observing inflammation factors.Results:Compared with the model group,the bee venom gelemicroneedle combination group can reduce the level of serum nitric oxide of the acute gouty inflammation model caused by sodium urate,and on LPS induced mouse model of acute inflammation effect and the micro.Conclusions:Bee venom can significantly suppress the occurrence of gouty arthritis inflammation in rats and mice LPS inflammatory reaction.Choose the 750 mm microneedle with 10N force on skin about 3 minutes,bee venom can play the optimal role,and the anti-inflammatory effect is obvious.Microneedles can promote the percutaneous absorption of the active macromolecules bee venom gel.展开更多
Objective:Current treatments for atrophic acne scars such as microneedling radiofrequency(MNRF)and fractional carbon dioxide(FCO_(2))laser have shown individual efficacy,but their combined effectiveness remains lackin...Objective:Current treatments for atrophic acne scars such as microneedling radiofrequency(MNRF)and fractional carbon dioxide(FCO_(2))laser have shown individual efficacy,but their combined effectiveness remains lacking.This study aimed to determine the effectiveness and safety of a sequential combination therapy with MNRF followed by FCO_(2) laser compared with each therapy administered alone for the treatment of atrophic acne scars.Methods:An open randomized trial was conducted on 45 patients with atrophic acne scars at Al-Salam Teaching Hospital,Mosul,Iraq,from January 2022 to July 2023.The patients were randomized into 3 groups,with 15 patients in each group:FCO_(2) group(6 sessions of FCO_(2) laser treatment),MNRF group(6 sessions of MNRF treatment),and combined group(3 sessions of MNRF treatment followed by 3 sessions of FCO_(2) laser treatment).The Goodman and Baron Global Quantitative Acne Scar Grading System(GBGQASGS)was used to assess the treatment effectiveness.Adverse effects of treatment were monitored.The pre-treatment and post-treatment GBGQASGS scores and the percentage reductions in the GBGQASGS scores in the 3 groups were assessed by analysis of variance.The effect size of each treatment regimen was assessed using the Cohen d effect size.Results:The 45 patients enrolled comprised 20(44.4%)men and 25(55.6%)women,with a mean age of 25.10±2.80 years and a GBGQASGS score of 28.93±6.19.All 3 types of treatment significantly reduced the GBGQASGS scores after 6 sessions(all P<0.05)as following:FCO_(2) group,from 28.66±5.71 to 11.66±2.71(59.3%reduction;Cohen d=3.80);MNRF group,from 27.26±6.93 to 11.66±3.09(57.2%reduction;Cohen d=2.90);Combined group,from 30.87±5.73 to 9.01±2.03(70.8%reduction;Cohen d=5.08).There was no difference in the GBGQASGS score of post-treatment among 3 groups(P=0.300),however,the combined group exhibited a significant reduction in the GBGQASGS score from pre-treatment to post-treatment(P<0.001).Post-inflammatory hyperpigmentation was reported in FCO_(2) and MNRF groups,tram-track scarring was found in FCO_(2) group,while no serious adverse effects were reported in the combined group.Conclusion:Sequential combination therapy with MNRF followed by FCO_(2) laser was as effective as each monotherapy for the treatment of atrophic acne scars with fewer adverse effects.The results may provide evidence for treatment choice.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
Aim:The aim of this literature review is to evaluate the efficacy of microneedling treatment with injectable platelet-rich fibrin(i-PRF)for facial skin rejuvenation applications,using an objective skin analysis system...Aim:The aim of this literature review is to evaluate the efficacy of microneedling treatment with injectable platelet-rich fibrin(i-PRF)for facial skin rejuvenation applications,using an objective skin analysis system and validated patient-reported outcome measures.Methods:The search approach involved the exploration of electronic databases.An advanced search option was applied to filter our search line,i.e.,from February 2011 to April 2021.We performed a search on Medline,Scopus,Embase,and Web of Science,while improving the accessed articles via Ovid interface.Our keywords were chiefly aligned with a combination of MeSH terms and text words.All retrieved articles were written in English.Results:The search yielded 73 studies.After reviewing their title and summary,nine of them were found to meet the inclusion criteria and,next,the full-text articles were reviewed.Of these,three studies were excluded from systematic research,as they would no longer meet the inclusion criteria.In total,six studies were considered for review.Conclusion:Microneedling treatments combined with blood concentrates are increasingly being utilized as autologous products for aesthetic purposes.Few works can be found on i-PRF in facial rejuvenation,and even fewer on i-PRF along with microneedling.Combined applications seem to be promising and minimally invasive.Further research on PRP and PRF is warranted to better elucidate their functional roles in medical cosmetic rejuvenation.展开更多
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
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-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
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
Psoriasis is a chronic inflammatory skin disease,which seriously affects the physical and mental health of patients.The progression of psoriasis is influenced by the excessive production of reactive oxygen species(ROS...Psoriasis is a chronic inflammatory skin disease,which seriously affects the physical and mental health of patients.The progression of psoriasis is influenced by the excessive production of reactive oxygen species(ROS)and inflammatory responses.In this paper,novel celastrol(Ce)-loaded metal-phenolic nanozymes(tannic acid-Fe^(3+))(TA-Fe)integrated microneedles(Ce@TA-Fe/MNs)were constructed to achieve the combined oxidative stress alleviation and anti-inflammatory therapy of psoriasis.Molecular dynamics simulations and structural characterization confirmed the successful fabrication of nanozymes.The Ce@TA-Fe/MNs system,characterized by its rapid dissolution kinetics and superior mechanical strength,enabled minimally invasive skin penetration for efficient nanozymes delivery.Nanozymes possessed superoxide dismutase and catalase mimetic enzyme activities,effectively eliminating excessive ROS in psoriatic skin lesions.Additionally,the release of Ce from Ce@TA-Fe provided strong antioxidant and anti-inflammatory effects.Based on these characteristics,Ce@TA-Fe/MNs could effectively alleviate the symptoms in psoriasis mice models.These findings demonstrated that the integration of Ce-equipped nanozymes within MNs holds great promise as a therapeutic strategy for the clinical management of psoriasis.展开更多
Acne vulgaris is one of the most common skin disorders affecting millions of patients worldwide,its long-lasting inflammation greatly reduces life quality and causes negative psychosocial impacts.Conventional treatmen...Acne vulgaris is one of the most common skin disorders affecting millions of patients worldwide,its long-lasting inflammation greatly reduces life quality and causes negative psychosocial impacts.Conventional treatments often along with side effects and issues of patient compliance,and ineffective in treating severe conditions.In recent years,microneedle(MN)has emerged as a versatile therapeutic technology,owing to its minimally invasive,effective,and reduced side effects.However,there are few review articles that systematically summarize the progress of microneedles for the treatment of acne.Here conclude the material,function,and application of microneedle technology in the treatment of acne,with a particular focus on two types of anti-acne microneedle:drug-loaded microneedle(DMN)and radio-frequency microneedle(RMN).DMN facilitates targeted drug delivery to the skin's deeper layers,while RMN utilizes radio-frequency currents to stimulate collagen regeneration,thus addressing acne scarring.Additionally,future directions for advanced acne-treating microneedle technology are envisioned,such as diversified drug loading,multi-functionality,production process optimization,and personalized treatment.These different directions are expected to further enhance the safety,efficacy,and patient satisfaction of microneedle acne treatments.展开更多
Microneedles(MNs)offer a precise and minimally invasive platform for delivering vaccines and therapeutic agents directly into the skin,leveraging the abundance of tissue-resident immune cells to elicit robust and dura...Microneedles(MNs)offer a precise and minimally invasive platform for delivering vaccines and therapeutic agents directly into the skin,leveraging the abundance of tissue-resident immune cells to elicit robust and durable immune responses.Compared to traditional intramuscular or subcutaneous vaccination methods,MNbased vaccines demonstrate superior patient compliance,enhanced antigen stability,and heightened immunogenicity,positioning them as a promising tool in biomedical applications.This review provides a comprehensive overview of the materials and fabrication techniques used in MN preparation,explores their structural classifications,and examines the role of antigens and adjuvants in optimizing vaccine efficacy.Furthermore,the diverse applications of MN delivery systems in preventing infectious diseases,advancing tumor immunotherapy,and addressing other immune-related conditions are discussed.展开更多
Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit,which brings serious physical and mental burden to patients.Despite decades of research,its pathogenesis remains multifactorial and incomplete...Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit,which brings serious physical and mental burden to patients.Despite decades of research,its pathogenesis remains multifactorial and incompletely elucidated.Conventional therapeutic approaches still have limitations in meeting clinical demands due to limited skin penetration,systemic side effects,and the emergence of antimicrobial resistance.Microneedles based drug delivery systems offer a minimally invasive strategy to overcome the stratum corneum barrier,achieve controlled intradermal drug release,and enhance local therapeutic efficacy while reducing systemic toxicity.This review systematically summarizes the latest research of microneedles for the treatment of acne.We first introduce the pathological mechanisms underlying acne development,followed by an overview of the latest advances in microneedle technologies for targeted acne therapy,including dissolving,hydrogel,solid,hollow,coated microneedles and stimuli-responsive designs.Finally,we highlight ongoing limitations and propose future strategies to enhance the development and clinical application of microneedle therapies in acne management.展开更多
Simultaneously suppressing tumor growth and metastasis is a pivotal strategy in the treatment of cutaneous melanoma(CM).Towards this end,we first developed a novel PtCu nanozyme(PtCu-zyme)integrating single-atom Pt an...Simultaneously suppressing tumor growth and metastasis is a pivotal strategy in the treatment of cutaneous melanoma(CM).Towards this end,we first developed a novel PtCu nanozyme(PtCu-zyme)integrating single-atom Pt and Pt subnanoclusters,which was further functionalized with triphenylphosphine(TPP)to yield PtCu-TPP and confer the nanozyme mitochondria-targeting capabilities.By combining PtCuTPP with a hyaluronic acid(HA)analog,isoliquiritigenin-grafted HA(HA-ISL),we later formulated PtCuTPP loaded microneedles(PtCu-TPP@MNs)for potent CM treatment.Our findings indicated that PtCuzyme exhibited exceptional oxidative enzyme-like properties and PtCu-TPP@MNs significantly inhibited the tumor growth and pulmonary metastasis.Furthermore,PtCu-TPP@MNs not only prolonged the survival of CM-bearing mice but also retained the nanozymes in the tumor,continually catalyzing reactive oxygen species(ROS)generation for sustained nanocatalytic therapy.In vitro studies revealed that PtCuTPP specifically localized within mitochondria,increasing ROS levels and causing mitochondrial damage,which in turn enhanced the cytotoxicity towards tumor cells.These findings suggest that PtCu-TPP@MN delivery system holds significant promise for the effective treatment of CM,potentially offering a valuable alternative to existing therapeutic strategies.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
Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several...Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several bottlenecks,including tumor heterogeneity,low immunogenicity,immunosuppressive tumor environment,and delivery obstacles,which collectively impact their clinical effectiveness.In this study,we developed nanocomposites containing positively charged melittin(MEL)and negatively charged photosensitizer indocyanine green(ICG),embedded in dissolving microneedles(MEL/ICG-HA@DMNs).This approach allows precise drug delivery by creating microchannels that bypass the stratum corneum barrier,targeting superficial lesions directly.Our results demonstrated that the complexation of MEL and ICG significantly reduced the hemolytic activity of MEL while maintaining its ability to disrupt cell membranes.After loading MEL/ICG-HA into the microneedle,MEL/ICG-HA@DMNs not only effectively concentrated the drug at the tumor site,inducing localized hyperthermia and successfully ablating the tumor,but also formed an in situ whole-cell vaccine containing a rich source of tumor-associated antigens.Moreover,the system promoted dendritic cell maturation and increased the M1/M2 macrophage ratio,enhancing the immune response.By overcoming the limitations of traditional cancer vaccines,this system ensures precise drug delivery and robust immune activation.This innovative approach holds the potential to revolutionize cancer treatment,offering a new paradigm in precision oncology.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
Melanoma is characterized by high malignancy,ranking the third among skin malignancies,and is associated with lack of specific treatment options and poor prognosis.Therefore,the development of effective therapies for ...Melanoma is characterized by high malignancy,ranking the third among skin malignancies,and is associated with lack of specific treatment options and poor prognosis.Therefore,the development of effective therapies for melanoma is imperative.A critical challenge in addressing subcutaneous disease lies in overcoming the skin barrier.In this study,we engineered a microneedle(MN)system that in-tegrates chemotherapy,photothermal therapy(PTT),and targeted therapy to enhance anti-tumor effi-cacy while effectively penetrating the skin barrier.In vitro studies have demonstrated that the MN drug delivery system(DDS)can effectively penetrate the stratum corneum of the skin,deliver therapeutics to subcutaneous tumor sites,and establish a drug reservoir at these locations to exert anti-tumor effects.Cellular experiments indicated that the engineered PTT chemotherapy-targeted MNs can be internalized by tumor cells,exhibiting enhanced cytotoxicity against them.In vivo pharmacological investigations revealed that the combination of PITT and chemotherapy delivered via this MN DDS produced synergistic anti-tumor effects,achieving a tumor inhibition rate of up to 98.15%.This in situ DDS minimizes involvement with other organs,significantly reducing chemotherapy-related side effects.In summary,the PTT chemotherapy-targeted MNs developed in this study demonstrate promising application po-tential by enhancing anti-tumor efficacy while minimizing adverse effects.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
Microneedle technology is valuable in wound treatment.Current studies focus on optimizing the function of microneedles and screening for effective encapsulated actives.Herein,we develop innovative MXene hydrogel micro...Microneedle technology is valuable in wound treatment.Current studies focus on optimizing the function of microneedles and screening for effective encapsulated actives.Herein,we develop innovative MXene hydrogel microneedles with nitric oxide(NO)and hypoxia-inducible factor-1α(HIF-1α)plasmid controllable release for diabetic wound treatment.These microneedles consist of gelatin coupled with tert-butyl nitrite(Gel-SNO)polymers obtained by conjugating the-SNO group on the gelatin side chain,therefore,NO can be generated and released under near-infra red(NIR)light irradiation owing to the thermal effect.Simultaneously,by harnessing the enhanced photothermal conversion efficiency of the MXene additive,the microneedle patch can quickly dissolve and liberate the enclosed HIF-1αplasmid nanoparticles into the dermis when exposed to NIR radiation.The released NO effectively reduced the inflammatory response and released HIF-1αplasmid induced neovascularization.Thus,in vivo experiments showed that these microneedles could accelerate wound closure by alleviating inflammation,and promoting re-epithelialization and angiogenesis.These results indicated the potential value of MXene hydrogel microneedles in wound healing and other related biomedical fields.展开更多
文摘Background and Objectives:Microneedling has been introduced as a new technique to address the growing concern of facial skin photoaging.Kangfuxin liquid has been found to promote the process of skin wound repair,including reducing inflammatory response,improving immunity and enhancing antioxidant levels.In this prospective randomized double-blinded study,we wanted to explore the clinical efficacy and safety of Kangfuxin liquid combined with microneedling in treating facial skin photoaging.Methods:57 patients with facial skin photoaging were randomly divided into two groups.The treatment group(28 cases)received microneedle therapy with Kangfuxin liquid,while the control group(29 cases)received microneedle therapy with physiological saline.The treatment interval was 4 weeks,and a total of 3 treatments were performed.Compare the VISIA scores of facial photoaging features such as wrinkles,texture,pores,spots and ultraviolet pigmentation between two groups of patients before and after treatment,Global Score for Photoaging,satisfaction evaluation,and record the occurrence of adverse reactions.Results:After treatment,the treatment group showed more significant improvement in wrinkles,texture,pores,spots and ultraviolet pigmentation,and the Global Score for Photoaging was better than the control group(P<0.05).The satisfaction rate with improving skin in the treatment group was 85.71%,which was higher than 75.86%in the control group(P<0.05).Both groups did not experience adverse reactions such as skin infection,pigmentation or hypopigmentation,scar formation,or worsening of melasma.Conclusion:Kangfuxin liquid combined with microneedling therapy has a good improvement effect on facial skin photoaging,with a low incidence of adverse reactions and high patient satisfaction.It is worthy of clinical promotion.
基金the Beijing Science and Technology New Star Program(grant No.2015A048)the Young Teacher Special of Beijing University of Chinese Medicine(1000061221025)National Science and Technology Major New Drug Projects(2014ZX09301306-009).
文摘Objective:To combine with transdermal drug delivery using microneedle to simulate the bee venom therapy to evaluate the permeation of bee venom gel.Methods:In this study,the sodium urate and LPS were used on rats and mice to construct the model.Bee venom gelemicroneedle combination effect on the model is to determine the role of microneedle gel permeation by observing inflammation factors.Results:Compared with the model group,the bee venom gelemicroneedle combination group can reduce the level of serum nitric oxide of the acute gouty inflammation model caused by sodium urate,and on LPS induced mouse model of acute inflammation effect and the micro.Conclusions:Bee venom can significantly suppress the occurrence of gouty arthritis inflammation in rats and mice LPS inflammatory reaction.Choose the 750 mm microneedle with 10N force on skin about 3 minutes,bee venom can play the optimal role,and the anti-inflammatory effect is obvious.Microneedles can promote the percutaneous absorption of the active macromolecules bee venom gel.
文摘Objective:Current treatments for atrophic acne scars such as microneedling radiofrequency(MNRF)and fractional carbon dioxide(FCO_(2))laser have shown individual efficacy,but their combined effectiveness remains lacking.This study aimed to determine the effectiveness and safety of a sequential combination therapy with MNRF followed by FCO_(2) laser compared with each therapy administered alone for the treatment of atrophic acne scars.Methods:An open randomized trial was conducted on 45 patients with atrophic acne scars at Al-Salam Teaching Hospital,Mosul,Iraq,from January 2022 to July 2023.The patients were randomized into 3 groups,with 15 patients in each group:FCO_(2) group(6 sessions of FCO_(2) laser treatment),MNRF group(6 sessions of MNRF treatment),and combined group(3 sessions of MNRF treatment followed by 3 sessions of FCO_(2) laser treatment).The Goodman and Baron Global Quantitative Acne Scar Grading System(GBGQASGS)was used to assess the treatment effectiveness.Adverse effects of treatment were monitored.The pre-treatment and post-treatment GBGQASGS scores and the percentage reductions in the GBGQASGS scores in the 3 groups were assessed by analysis of variance.The effect size of each treatment regimen was assessed using the Cohen d effect size.Results:The 45 patients enrolled comprised 20(44.4%)men and 25(55.6%)women,with a mean age of 25.10±2.80 years and a GBGQASGS score of 28.93±6.19.All 3 types of treatment significantly reduced the GBGQASGS scores after 6 sessions(all P<0.05)as following:FCO_(2) group,from 28.66±5.71 to 11.66±2.71(59.3%reduction;Cohen d=3.80);MNRF group,from 27.26±6.93 to 11.66±3.09(57.2%reduction;Cohen d=2.90);Combined group,from 30.87±5.73 to 9.01±2.03(70.8%reduction;Cohen d=5.08).There was no difference in the GBGQASGS score of post-treatment among 3 groups(P=0.300),however,the combined group exhibited a significant reduction in the GBGQASGS score from pre-treatment to post-treatment(P<0.001).Post-inflammatory hyperpigmentation was reported in FCO_(2) and MNRF groups,tram-track scarring was found in FCO_(2) group,while no serious adverse effects were reported in the combined group.Conclusion:Sequential combination therapy with MNRF followed by FCO_(2) laser was as effective as each monotherapy for the treatment of atrophic acne scars with fewer adverse effects.The results may provide evidence for treatment choice.
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 an institutional grant of the University of Camerino.
文摘Aim:The aim of this literature review is to evaluate the efficacy of microneedling treatment with injectable platelet-rich fibrin(i-PRF)for facial skin rejuvenation applications,using an objective skin analysis system and validated patient-reported outcome measures.Methods:The search approach involved the exploration of electronic databases.An advanced search option was applied to filter our search line,i.e.,from February 2011 to April 2021.We performed a search on Medline,Scopus,Embase,and Web of Science,while improving the accessed articles via Ovid interface.Our keywords were chiefly aligned with a combination of MeSH terms and text words.All retrieved articles were written in English.Results:The search yielded 73 studies.After reviewing their title and summary,nine of them were found to meet the inclusion criteria and,next,the full-text articles were reviewed.Of these,three studies were excluded from systematic research,as they would no longer meet the inclusion criteria.In total,six studies were considered for review.Conclusion:Microneedling treatments combined with blood concentrates are increasingly being utilized as autologous products for aesthetic purposes.Few works can be found on i-PRF in facial rejuvenation,and even fewer on i-PRF along with microneedling.Combined applications seem to be promising and minimally invasive.Further research on PRP and PRF is warranted to better elucidate their functional roles in medical cosmetic rejuvenation.
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 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 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 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 Key Research Project of the Educational Department of Liaoning Province,China(JYTZD2023139).
文摘Psoriasis is a chronic inflammatory skin disease,which seriously affects the physical and mental health of patients.The progression of psoriasis is influenced by the excessive production of reactive oxygen species(ROS)and inflammatory responses.In this paper,novel celastrol(Ce)-loaded metal-phenolic nanozymes(tannic acid-Fe^(3+))(TA-Fe)integrated microneedles(Ce@TA-Fe/MNs)were constructed to achieve the combined oxidative stress alleviation and anti-inflammatory therapy of psoriasis.Molecular dynamics simulations and structural characterization confirmed the successful fabrication of nanozymes.The Ce@TA-Fe/MNs system,characterized by its rapid dissolution kinetics and superior mechanical strength,enabled minimally invasive skin penetration for efficient nanozymes delivery.Nanozymes possessed superoxide dismutase and catalase mimetic enzyme activities,effectively eliminating excessive ROS in psoriatic skin lesions.Additionally,the release of Ce from Ce@TA-Fe provided strong antioxidant and anti-inflammatory effects.Based on these characteristics,Ce@TA-Fe/MNs could effectively alleviate the symptoms in psoriasis mice models.These findings demonstrated that the integration of Ce-equipped nanozymes within MNs holds great promise as a therapeutic strategy for the clinical management of psoriasis.
基金support from the College Students’Innovative Entrepreneurial Training Plan Program(Northwestern Polytechnical University),the National Natural Science Foundation of China(No.52473265)the Shaanxi Provincial Science Fund for Distinguished Young Scholars(No.2023-JC-JQ-32).
文摘Acne vulgaris is one of the most common skin disorders affecting millions of patients worldwide,its long-lasting inflammation greatly reduces life quality and causes negative psychosocial impacts.Conventional treatments often along with side effects and issues of patient compliance,and ineffective in treating severe conditions.In recent years,microneedle(MN)has emerged as a versatile therapeutic technology,owing to its minimally invasive,effective,and reduced side effects.However,there are few review articles that systematically summarize the progress of microneedles for the treatment of acne.Here conclude the material,function,and application of microneedle technology in the treatment of acne,with a particular focus on two types of anti-acne microneedle:drug-loaded microneedle(DMN)and radio-frequency microneedle(RMN).DMN facilitates targeted drug delivery to the skin's deeper layers,while RMN utilizes radio-frequency currents to stimulate collagen regeneration,thus addressing acne scarring.Additionally,future directions for advanced acne-treating microneedle technology are envisioned,such as diversified drug loading,multi-functionality,production process optimization,and personalized treatment.These different directions are expected to further enhance the safety,efficacy,and patient satisfaction of microneedle acne treatments.
基金supported by the National Science Fund for National Natural Science Foundation of China(Grant Nos.22232006,22377127,and 52361145848)Chinese Academy of Sciences(CAS)Project for Young Scientists in Basic Research(Grant No.YSBR-083)+2 种基金the Beijing Nova Program(Grant Nos.20230484352 and 20240484650)Institute of Process Engineering Project for Frontier Basic Research(Grant No.QYJC-2023-05)Progress of Strategy Priority Research Program(Category B)of CAS(Grant No.XDB0520300).
文摘Microneedles(MNs)offer a precise and minimally invasive platform for delivering vaccines and therapeutic agents directly into the skin,leveraging the abundance of tissue-resident immune cells to elicit robust and durable immune responses.Compared to traditional intramuscular or subcutaneous vaccination methods,MNbased vaccines demonstrate superior patient compliance,enhanced antigen stability,and heightened immunogenicity,positioning them as a promising tool in biomedical applications.This review provides a comprehensive overview of the materials and fabrication techniques used in MN preparation,explores their structural classifications,and examines the role of antigens and adjuvants in optimizing vaccine efficacy.Furthermore,the diverse applications of MN delivery systems in preventing infectious diseases,advancing tumor immunotherapy,and addressing other immune-related conditions are discussed.
基金The National Natural Science Foundation of China(52403189)the Natural Science Foundation of Jiangsu Province(BK20220170)the Wenzhou Institute UCAS startup fund(WIUCASQD2024009).
文摘Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit,which brings serious physical and mental burden to patients.Despite decades of research,its pathogenesis remains multifactorial and incompletely elucidated.Conventional therapeutic approaches still have limitations in meeting clinical demands due to limited skin penetration,systemic side effects,and the emergence of antimicrobial resistance.Microneedles based drug delivery systems offer a minimally invasive strategy to overcome the stratum corneum barrier,achieve controlled intradermal drug release,and enhance local therapeutic efficacy while reducing systemic toxicity.This review systematically summarizes the latest research of microneedles for the treatment of acne.We first introduce the pathological mechanisms underlying acne development,followed by an overview of the latest advances in microneedle technologies for targeted acne therapy,including dissolving,hydrogel,solid,hollow,coated microneedles and stimuli-responsive designs.Finally,we highlight ongoing limitations and propose future strategies to enhance the development and clinical application of microneedle therapies in acne management.
基金support by the National Natural Science Foundation of China(Nos.82172591 and 81573011)。
文摘Simultaneously suppressing tumor growth and metastasis is a pivotal strategy in the treatment of cutaneous melanoma(CM).Towards this end,we first developed a novel PtCu nanozyme(PtCu-zyme)integrating single-atom Pt and Pt subnanoclusters,which was further functionalized with triphenylphosphine(TPP)to yield PtCu-TPP and confer the nanozyme mitochondria-targeting capabilities.By combining PtCuTPP with a hyaluronic acid(HA)analog,isoliquiritigenin-grafted HA(HA-ISL),we later formulated PtCuTPP loaded microneedles(PtCu-TPP@MNs)for potent CM treatment.Our findings indicated that PtCuzyme exhibited exceptional oxidative enzyme-like properties and PtCu-TPP@MNs significantly inhibited the tumor growth and pulmonary metastasis.Furthermore,PtCu-TPP@MNs not only prolonged the survival of CM-bearing mice but also retained the nanozymes in the tumor,continually catalyzing reactive oxygen species(ROS)generation for sustained nanocatalytic therapy.In vitro studies revealed that PtCuTPP specifically localized within mitochondria,increasing ROS levels and causing mitochondrial damage,which in turn enhanced the cytotoxicity towards tumor cells.These findings suggest that PtCu-TPP@MN delivery system holds significant promise for the effective treatment of CM,potentially offering a valuable alternative to existing therapeutic strategies.
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 the National Natural Science Foundation of China(Nos.82173747,82373803)the Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province(No.2021TQ060944)。
文摘Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several bottlenecks,including tumor heterogeneity,low immunogenicity,immunosuppressive tumor environment,and delivery obstacles,which collectively impact their clinical effectiveness.In this study,we developed nanocomposites containing positively charged melittin(MEL)and negatively charged photosensitizer indocyanine green(ICG),embedded in dissolving microneedles(MEL/ICG-HA@DMNs).This approach allows precise drug delivery by creating microchannels that bypass the stratum corneum barrier,targeting superficial lesions directly.Our results demonstrated that the complexation of MEL and ICG significantly reduced the hemolytic activity of MEL while maintaining its ability to disrupt cell membranes.After loading MEL/ICG-HA into the microneedle,MEL/ICG-HA@DMNs not only effectively concentrated the drug at the tumor site,inducing localized hyperthermia and successfully ablating the tumor,but also formed an in situ whole-cell vaccine containing a rich source of tumor-associated antigens.Moreover,the system promoted dendritic cell maturation and increased the M1/M2 macrophage ratio,enhancing the immune response.By overcoming the limitations of traditional cancer vaccines,this system ensures precise drug delivery and robust immune activation.This innovative approach holds the potential to revolutionize cancer treatment,offering a new paradigm in precision oncology.
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the Natural Science Foundation of Xiamen,China(Grant No.:3502z20227074)NaturalScience Foundation of Fujian Province,China(Grant Nos.:2022J011405, 2022J05320)+1 种基金Fujian College Student Innovation and Entrepreneurship Training Program(Program No.:202312631008)National College Student Innovation and Entrepreneurship Training Program(Program No.:202312631003).
文摘Melanoma is characterized by high malignancy,ranking the third among skin malignancies,and is associated with lack of specific treatment options and poor prognosis.Therefore,the development of effective therapies for melanoma is imperative.A critical challenge in addressing subcutaneous disease lies in overcoming the skin barrier.In this study,we engineered a microneedle(MN)system that in-tegrates chemotherapy,photothermal therapy(PTT),and targeted therapy to enhance anti-tumor effi-cacy while effectively penetrating the skin barrier.In vitro studies have demonstrated that the MN drug delivery system(DDS)can effectively penetrate the stratum corneum of the skin,deliver therapeutics to subcutaneous tumor sites,and establish a drug reservoir at these locations to exert anti-tumor effects.Cellular experiments indicated that the engineered PTT chemotherapy-targeted MNs can be internalized by tumor cells,exhibiting enhanced cytotoxicity against them.In vivo pharmacological investigations revealed that the combination of PITT and chemotherapy delivered via this MN DDS produced synergistic anti-tumor effects,achieving a tumor inhibition rate of up to 98.15%.This in situ DDS minimizes involvement with other organs,significantly reducing chemotherapy-related side effects.In summary,the PTT chemotherapy-targeted MNs developed in this study demonstrate promising application po-tential by enhancing anti-tumor efficacy while minimizing adverse effects.
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 Key Research and Development Program of China(2022YFA1105300)the Key Research&Developement(R&D)Program of Jiangsu Province(BE2022853)+2 种基金the Joint Fund of Henan Province Science and Technology R&D Program(225200810021)the Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-01)theJiangsu Funding Program for Excellent Postdoctoral Talent(2024ZB003)。
文摘Microneedle technology is valuable in wound treatment.Current studies focus on optimizing the function of microneedles and screening for effective encapsulated actives.Herein,we develop innovative MXene hydrogel microneedles with nitric oxide(NO)and hypoxia-inducible factor-1α(HIF-1α)plasmid controllable release for diabetic wound treatment.These microneedles consist of gelatin coupled with tert-butyl nitrite(Gel-SNO)polymers obtained by conjugating the-SNO group on the gelatin side chain,therefore,NO can be generated and released under near-infra red(NIR)light irradiation owing to the thermal effect.Simultaneously,by harnessing the enhanced photothermal conversion efficiency of the MXene additive,the microneedle patch can quickly dissolve and liberate the enclosed HIF-1αplasmid nanoparticles into the dermis when exposed to NIR radiation.The released NO effectively reduced the inflammatory response and released HIF-1αplasmid induced neovascularization.Thus,in vivo experiments showed that these microneedles could accelerate wound closure by alleviating inflammation,and promoting re-epithelialization and angiogenesis.These results indicated the potential value of MXene hydrogel microneedles in wound healing and other related biomedical fields.
