The complex skin structure and insufficient intracellular entrapment limit the therapeutic effects of active substances,therefore appealing to a more effective transdermal drug delivery system design.Herein,a hyaluron...The complex skin structure and insufficient intracellular entrapment limit the therapeutic effects of active substances,therefore appealing to a more effective transdermal drug delivery system design.Herein,a hyaluronic acid(HA)modified steareth-2-based niosomes(HA-nio)with satisfactory deformability and targeting properties was designed for ergothioneine(EGT)(EGT@HA-nio)against ultraviolet(UV)-induced skin damage.The unique composition allows EGT@HA-nio to exhibit high mechanical softness,making it deformable to pass through the stratum corneum by the intercellular space without rupture.For further intracellular delivery,HA modification enables EGT to target human dermal cells(HDFs)with increased distribution in mitochondria without the restriction of specific EGT transporter-organic cation transporter1(OCTN-1).Benefiting from the above properties,an adequate amount of EGT in the active form was accumulated in the desired cellular sites,alleviating UV-radiation-induced reactive oxygen species(ROS)generation,inflammatory factor release,DNA damage,and mitochondrial dysfunction.The in vivo experimental results show that EGT@HA-nio could significantly decrease collagen degradation,restore epidermal thickness and morphology to healthy levels,and effectively prevent UV-induced skin damage.With the ability to penetrate biological barriers and deliver drugs,HA-nio may promote the development of inadequate drug penetration disease treatment including skin diseases,cancers,and bacterial infections.展开更多
Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inh...Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inhibits Candida albicans.AmB is primarily administered via oral and intravenous infusion,but severe infusion adverse effects,nephrotoxicity,and potential hepatotoxicity limit its clinical application.Deep eutectic solvents(DESs),with excellent solubilization ability and skin permeability,are attractive for transdermal delivery.Herein,we used DESs to deliver AmB for antifungal therapy transdermally.We first prepared and characterized DESs with different stoichiometric ratios of choline(Ch)and geranate(Ge).DESs increased the solubility of AmB by a thousand-fold.In vitro and in vivo,skin permeation studies indicated that DES_(1:2)(Ch and Ge in 1:2 ratio)had the most outstanding penetration and delivered fluorescence dye to the dermis layer.Then,DES_(1:2)-AmB was prepared and in vitro antifungal tests demonstrated that DES_(1:2)-AmB had superior antifungal effects compared to AmB and DES_(1:2).Furthermore,DES_(1:2)-AmB was skin-irritating and biocompatible.In conclusion,DES-AmB provides a new and effective therapeutic solution for fungal infections.展开更多
One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transderm...One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transdermal delivery of docetaxel （DTX）, a model drug for high molecular weight and poorly water-soluble drugs. Surfactant-ethanolic liposomes （SEL） were composed of phospholipids, ethanol, sodium cholate, DTX and PBS which were prepared by thin film dispersion method. The developed formulations were characterized by determining the vesicle shape and surface morphology, size and size distribution, entrapment efficiency and drug loading capacity. The effects of the developed formulations on the permeation of DTX across rat skin in vitro were investigated using the modified Franz diffusion cell under both occlusive and non-occlusive application condi- tions. The DTX SELs with optimum composition （phospholipid-surfactant, 85：15, w/w） provided a significantly higher steadystate amount of flux and cumulative permeation, compared to the tranditional liposomes, surfactant liposomes and ethanolic liposomes. The optimal SELs exhibited stable vesicle size, morphology and drug loading capacity. Our results indicated that SELs were promising carriers to enhance the transdermal delivery of DTX.展开更多
Aim To study the influence of electric field direction on the in vitro enhanced transdermal delivery of caffeine by eleetroporation. Methods Using side-by-side compartment diffusion cells method and Ag-Ag/AgCl electro...Aim To study the influence of electric field direction on the in vitro enhanced transdermal delivery of caffeine by eleetroporation. Methods Using side-by-side compartment diffusion cells method and Ag-Ag/AgCl electrodes, the transport of caffeine through human cadaver skin by electroporation （exponentially decaying pulse, pulse voltage = 350 V, pulse frequency = 4 pulses· min^-1, capacity = 22 μF, pulse length = 7 ms, 25 pulses） with different electric field directions was carried out and compared with passive diffusion and iontophoresis （0.25 mA·cm^ - 2, lasted for 4 h）. Results （i） The cumulative quantity and flux of caffeine through human skin were increased significantly by eleetroporation or iontophoresis. （ii） The transport of caffeine by positive iontophoresis （ with electric field from donor to receptor compartment） was significantly greater than that by negative iontophoresis （with electric field from receptor to donor compartment）. （iii） The transport of caffeine by positive eleetroporation （with electric field from donor to receptor compartment） was similar to that by negative eleetroporation （with electric field from receptor to donor compartment）. （iv） The enhancing effect of positive iontophoresis on the transdermal delivery of caffeine was significantly greater than that of electroporation （positive or negative）. Conclusion Electric field direction significantly influences the enhancing effect of iontophoresis on the transdermal delivery of caffeine, but does not influence the enhancing effect of eleetroporation.展开更多
Aim Liposomal fluconazole gel was prepared and its properties were studied. Methods The fluconazole liposomes were prepared by film dispersion method. Their shapes and sizes were observed by transmission electronic mi...Aim Liposomal fluconazole gel was prepared and its properties were studied. Methods The fluconazole liposomes were prepared by film dispersion method. Their shapes and sizes were observed by transmission electronic microscope and particle size analyzer, respectively. The skin permeation of liposomal gel was studied on rat skin by permeation cell. Results The entrapment efficiency of flueonazole liposomes was 47.68%. The fluconazole liposomes were oval or round in shape, and their average diameter was 250 ± 8 nm. The accumulative skin permeation of liposomal fluconazole gel （25.27%） was lower than that of non-liposomal fluconazole gel （36.72%）, but fluconazole retained in rat skin of liposomal gel （162 ± 15 μg·cm^-2） was higher than that of nonliposomal gel （48 ± 6μg·cm^-2）. Conclusion Liposomal fluconazole gel can significantly increase the deposited amounts of fluconazole in rat skin and it may be beneficial for topical use.展开更多
Injection therapy for diabetes has poor patient compliance,and the pain occurring at the site of subcutaneous injections causes significant inconvenience to diabetic patients.In this work,to demonstrate the benefits o...Injection therapy for diabetes has poor patient compliance,and the pain occurring at the site of subcutaneous injections causes significant inconvenience to diabetic patients.In this work,to demonstrate the benefits of an alternative drug delivery technique that overcomes these issues,methacrylated gelatin hydrogel-forming microneedles integrated with metformin were developed to adjust blood glucose levels in diabetic rats.Gelatin methacryloyl microneedles(GelMA-MNs)with different degrees of substitution were successfully prepared by a micro-molding method.The resultant GelMA-MNs exhibited excellent mechanical properties and moisture resistance.Metformin,an anti-diabetic drug,was further encapsulated into the GelMA-MNs,and its release rate could be controlled by the three-dimensional cross-linked network of microneedles,thereby exhibiting sustained drug release behaviors in vitro and implying a better therapeutic effect compared with that of subcutaneous injection in diabetic rats.The drug release period could be significantly prolonged by improving the cross-link density of GelMA-MNs.The results of hypoglycemic effect evaluation show that the application of GelMA-MNs for transdermal delivery in diabetic rats has promising benefits for diabetes treatment.展开更多
Microemulsion systems, composed of water, isopropyl myristate （IPM）, polyoxyethylene sorbitan trioleate （Tween 85 ）, and ethanol, were investigated as transdermal drug delivery vehicles for a lipophilic model drug...Microemulsion systems, composed of water, isopropyl myristate （IPM）, polyoxyethylene sorbitan trioleate （Tween 85 ）, and ethanol, were investigated as transdermal drug delivery vehicles for a lipophilic model drug（ meloxicam）. The purpose of this study was to investigate the physicochemieal properties of the tested microemulsion and to find the correlation between the physicoehemical properties and the skin permeation rate of the microemulsion. Pseudo-ternary phase diagram of the investigated system at a constant surfactant/cosurfactant mass ratio （ Km = 1 ： 1 ） was constructed by titration at 20℃, and the five fommlations were selected for further research in the o/w microemulsion domains. The values of electrical conductivity and viscosity showed that the selected systems were bicontinuous or non-spherical o/w microemulsion, and the electrical conductivity and viscosity were increased with increasing the content of water. These results suggest that the optimum formulation of microemulsion, containing 0. 375 meloxicam, 5% isopropyl myristate, 25% Tween 85. 25% ethanol, and water, showed the maximum permeation rate. It had a high electrical conductivity, small droplet size, and proper viscocity.展开更多
Objective: To report the influence of transdermal delivery of asiatic acid(AA) in Plasmodium berghei-infected Sprague Dawley rats on physicochemical changes, %parasitaemia and associated pathophysiology. Methods: A to...Objective: To report the influence of transdermal delivery of asiatic acid(AA) in Plasmodium berghei-infected Sprague Dawley rats on physicochemical changes, %parasitaemia and associated pathophysiology. Methods: A topical once-off AA(5, 10, and 20 mg/kg)- or chloroquine(CHQ)-pectin patch was applied on the shaven dorsal neck region of Plasmodium berghei-infected Sprague Dawley rats(90-120 g) on day 7 after infection. Eating and drinking habits, weight changes, malaria effects and %parasitaemia were compared among animal groups over 21 d. Results: AA-pectin patch application preserved food and water intake together with %weight gain. All animals developed stable parasitaemia(15%-20%) by day 7. AA doses suppressed parasitaemia significantly. AA 5 mg/kg patch was most effective. AA and CHQ displayed bimodal time-spaced peaks. CHQ patch had a longer time course to clear parasitaemia. Conclusions: AA influences bio-physicochemical changes and parasitaemia suppression in dose dependent manner. In comparison by dose administered, AA has much better efficacy than CHQ. AA may be a useful antimalarial. AA and CHQ displays bimodal peaks suggesting possible synergism if used in combination therapy.展开更多
Diabetic pressure ulcers(DPU)are non-healing due to vascular dysfunction and bacterial infection.Early intervention can delay ulcer progression,such as preventing the formation of full-thickness skin defects.Local adm...Diabetic pressure ulcers(DPU)are non-healing due to vascular dysfunction and bacterial infection.Early intervention can delay ulcer progression,such as preventing the formation of full-thickness skin defects.Local administration of deferoxamine(DFO)at wound sites has been shown to promote neovascularization and enhance wound healing.However,since DPU skin wounds are not full-thickness defects and DFO is hydrophilic,enhancing its transdermal delivery is crucial for effective treatment.Photothermal ablation of stratum corneum,generated by copper sulfide nanoparticles(Cu S NPs)under near-infrared(NIR)light irradiation,is a promising method to improve transdermal drug delivery.Meanwhile,Cu S NPs-induced photothermal therapy offers excellent antibacterial performance.In this study,DFO and Cu S NPs were incorporated into a matrix metalloproteinase(MMPs)-sensitive hydrogel.This hydrogel promotes cell adhesion and is degraded by cell-secreted MMPs,a process crucial for the controlled release of encapsulated DFO and Cu S NPs.Under NIR irradiation,the stratum corneum is disrupted,facilitating transdermal DFO delivery and simultaneously eliminating infected bacteria.As a result,the essential requirements for DPU treatment,“facilitating transdermal DFO delivery,promoting angiogenesis,and inhibiting bacterial infection”,were achieved simultaneously.展开更多
This study aimed to evaluate the patient-friendly methods that are used in the delivery of hydrophilic macromolecules into deep skin layers,in particular,the combination of microneedles patch(MNs patch)and low-frequen...This study aimed to evaluate the patient-friendly methods that are used in the delivery of hydrophilic macromolecules into deep skin layers,in particular,the combination of microneedles patch(MNs patch)and low-frequency sonophoresis(SN).The hydrophilic macromolecule drug fluorescein isothiocyanate(FITC)-dextrans(FD-4:MW 4.4 kDa)was used as the model drug in our experimental design.In this study,excised porcine skin was used to investigate and optimize the key parameters that determine effective MNs-and SNfacilitated FD-4 delivery.In vitro skin permeation experiments revealed that the combination of MNs patch with SN had a superior enhancing effect of skin permeation for FD-4 compared to MNs alone,SN alone or untreated skin,respectively.The optimal parameters for the combination of MNs and SN included the following:10 N insertion force of MNs,4 W/cm^(2)SN intensity,6 mm radiation diameter of the SN probe,2 min application time,and the continuous mode duty cycle of SN.In addition,vertical sections of skin,clearly observed under a confocal microscope,confirmed that the combination of MNs and SN enhanced permeation of FD-4 into the deep skin layers.These studies suggest that the combination of MNs and SN techniques could have great potential in the delivery of hydrophilic macromolecules into deep skin.展开更多
Atopic dermatitis(AD) is a chronic inflammatory skin condition. Natural products have gained traction in AD treatment due to their accessibility, low toxicity, and favorable pharmacological properties. However, their ...Atopic dermatitis(AD) is a chronic inflammatory skin condition. Natural products have gained traction in AD treatment due to their accessibility, low toxicity, and favorable pharmacological properties. However, their application is primarily constrained by poor solubility, instability, and limited permeability. The transdermal drug delivery system(TDDS) offers potential solutions for transdermal delivery, enhanced penetration, improved efficacy, and reduced toxicity of natural drugs, aligning with the requirements of modern AD treatment. This review examines the application of hydrogels, microneedles(MNs), liposomes, nanoemulsions, and other TDDS-carrying natural products in AD treatment, with a primary focus on their effects on penetration and accumulation in the skin. The aim is to provide valuable insights into the treatment of AD and other dermatological conditions.展开更多
The traditional Chinese medicine tripterygium glycosides(TPG)is used clinically to treat some Rheumatism,Eczema,immunosuppression and tumor,with the activities of hypnosis,antipyretic,analgesic,antiinflammatory,allerg...The traditional Chinese medicine tripterygium glycosides(TPG)is used clinically to treat some Rheumatism,Eczema,immunosuppression and tumor,with the activities of hypnosis,antipyretic,analgesic,antiinflammatory,allergy and antitumor.However TPG has low water solubility and low skin permeability,so its clinical use is limited.Transdermal delivery systems can provide a controlled drug release rate that can keep constant concentrations of drug in the plasma for up to multiple days,improved patient compliance,and the possibility ofreducing the rate and severity of side effects.In this study,a fast and sensitive technique skin-blood two sites synchronous microdialysis coupled with LC-MS was used to study the pharmacokinetic parameter of three different formulations(TPG nanoemulsion,TPG nanoemulsion based gels and TPG gel).Creating a multilayer model,use the model to simulate the three formulations dynamics in transdermal-drug delivery system.The experiment results showed that the TPG nanoemulsion,TPG nanoemulsion based gels can significantly raise the drug concentrations in skin more than that of TPG gels.The numerical simulation results indicating that TPG gel and TPG nanoemulsion are close to practical measurements,only in the concentration increase phase the numerical simulation result has some difference with the experimental results.TPG nanoemulsion based gels have significant difference with the experimental results,both in concentration increase stage and concentration decreasing stage,but its trend was same.The study shows that the skin-blood synchronous microdialysis technique provided a new method for the pharmacokinetics study of nanocarriers transdermal delivery systems.In addition,the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery system.展开更多
Epinephrine is important for first aid and usually applied via injection,which is painful and problematic in operation,thereby making it difficult to self-delivery.In this study,a method to actively transdermal delive...Epinephrine is important for first aid and usually applied via injection,which is painful and problematic in operation,thereby making it difficult to self-delivery.In this study,a method to actively transdermal delivery of epinephrine is proposed based on incorporating microneedles with iontophoresis,and then a wearable device is fabricated for rapid and controllable self-delivery of epinephrine.The device consists of a hydrogel microneedle array,a conductive drug delivery hydrogel,iontophoresis electrodes,and an encapsulated cartridge with a spring and self-locking micro-mechanism.The microneedles create subcutaneous microchannels,allowing the epinephrine contained in the hydrogel to enter the body under the control of iontophoretic currents.The dosage and rate can be adjusted at different levels by pressing the button so that it can be used by different groups of people for rapid self-aid and recovery from fatigue.The device can be worn in advance if required.In-vitro tests showed that the transdermal delivery rate of the device was between 0.02642 and 0.1059 mg/h cm^(2).As a proof-of-concept application,in-vivo experiments showed that the device could reverse life-threatening shock reactions in a piglet model of hemorrhagic shock through the delivery of epinephrine.展开更多
Endometrial injury and resulting female infertility pose significant clinical challenges due to the notable shortcomings of traditional treatments.Herein,we proposed a double network composite hydrogel,CSMA-RCZn-PNS,w...Endometrial injury and resulting female infertility pose significant clinical challenges due to the notable shortcomings of traditional treatments.Herein,we proposed a double network composite hydrogel,CSMA-RCZn-PNS,which forms a physical barrier on damaged tissue through photo-crosslinking while enabling sus-tained release of the active ingredient PNS.Based on this,we developed a combined strategy to enhance transdermal delivery efficiency using ultrasound cavitation.In vitro experiments demonstrated that CSMA-RC-Zn-PNS exhibits excellent biosafety,biodegradability,and promotes cell proliferation,migration,and tube forma-tion,along with antioxidant and antibacterial properties.In a rat endometrial injury model,the ultrasound cavitation effect was demonstrated to enhance transdermal delivery efficiency,and the ability of CSMA-RC-Zn-PNS to promote endometrial regeneration,anti-fibrosis and fertility restoration was verified.Overall,this strategy combining CSMA-RC-Zn-PNS hydrogel and ultrasound treatment shows promising applications in endometrial regeneration and female reproductive health.展开更多
Transdermal drug delivery offers the benefits of first-pass metabolism avoidance,high bioavailability,a low dose,and high patient compliance.Ethosomes are lipid-based vesicles containing phospholipids,ethanol,and wate...Transdermal drug delivery offers the benefits of first-pass metabolism avoidance,high bioavailability,a low dose,and high patient compliance.Ethosomes are lipid-based vesicles containing phospholipids,ethanol,and water that enhance drug penetration by overcoming the barrier of the skin.Ethosomes can encapsulate lipophilic as well as hydrophilic drugs to increase their efficacy.Zingerone(ZNE)is a major component found in gingerroot and has potent antidiabetic,antioxidant,and antispasmodic activities.ZNE has low solubility in aqueous media,which leads to low oral bioavailability.ZNE-loaded ethosomes were prepared via the cold method.The ethosomes were optimized by a 3-level and 2-factor full factorial design.The independent variables selected were ethanol(%)and soy lecithin(%).The dependent variables selected were flux(μg/cm^(2)/h)and entrapment efficiency(%).The optimized formulation was evaluated for size,polydispersity index,zeta potential,entrapment efficiency,in vitro drug release,and ex vivo skin drug permeation.The optimized formulation had an average vesicle size of 77.12±1.89 nm,a polydispersity index of 0.350±0.013,a zeta potential of -56.9±1.25 mV,an entrapment efficiency of 75.83%±1.53%,in vitro drug release of 85.97%±1.92%(after 24 h),and ex vivo skin drug permeation of 78.52%±1.62%.The optimized formulation was converted to a gel formulation and characterized for in vitro parameters.The percent permeation of ZNE through rat skin(ex vivo)from the ethosomal gel was greater(73.12%±1.76%)than that from the conventional gel(38.17%±1.82%).This study reveals the substantial potential of ZNE-loaded ethosomes for transdermal delivery and for use in the management of systemic diseases.展开更多
The global burden of cancer, a progressive disease with complex etiology, continues to rise. With an estimated 1.5 million new diagnoses each year, including nearly 350 000 cases of highly aggressive melanoma, the nee...The global burden of cancer, a progressive disease with complex etiology, continues to rise. With an estimated 1.5 million new diagnoses each year, including nearly 350 000 cases of highly aggressive melanoma, the need for improved therapeutic strategies is paramount. The World Health Organization(WHO) and the International Labour Organization have established a clear link between occupational exposure to solar ultraviolet radiation(UVR) and increased risk of non-melanoma skin cancer(NMSC). While age, skin tone, and cumulative UVR exposure are recognized risk factors, current treatment modalities, including chemotherapy and surgery, often exhibit limited efficacy and significant side effects. This underscores the urgent need for novel therapeutic approaches that enable targeted drug delivery, enhanced tumor penetration, and reduced systemic toxicity. Transferosomes-based drug delivery systems have emerged as a promising avenue for achieving these goals, with vesicular systems offering a particularly attractive strategy for transdermal skin cancer therapy. This review focuses on transferosomes and transethosomes as such vesicular systems, highlighting recent advances in their application for targeted skin cancer treatment.展开更多
Transdermal drug delivery(TDD)systems have evolved,with skin electronics emerging as a technology capable of enabling efficient drug administration.However,conventional skin electronics often rely on rigid materials a...Transdermal drug delivery(TDD)systems have evolved,with skin electronics emerging as a technology capable of enabling efficient drug administration.However,conventional skin electronics often rely on rigid materials and expensive fabrication processes,limiting flexibility and skin-adhesion.In this study,we developed cellulose nanofiber(CNFs)-based adhesive electronics by integrating a three-dimensional octopus-inspired architecture(OIA)and a conductive layer.The OIA imprinted on CNFs enhanced adhesion by leveraging the synergistic effect of its adhesive structure and the ability to remain stable even after absorbing active ingredient solutions.Unlike conventional fiber-based TDD platforms,the optimized CNFs-OIA retains its architecture,enabling suction-based adhesion to improve skin attachment.To further enhance the TDD efficiency,we integrated a conductive layer into the CNFs-OIA.This conductive interface generates microcurrents that reduce the electrical resistance of the stratum corneum and facilitates the ionization of active ingredients,thereby improving skin penetration.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
Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN...Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.展开更多
Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to ...Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to lose efficacy over prolonged applications.Traditional Chinese medicine(TCM)offers as a promising candidate to treat pathological scars.A large number of TCMs have been studied to show anti-scarring effect,however,the natural barrier of the skin impedes their penetration,lowering its therapeutic efficacy.Herein,we reported the use of dissolvable hyaluronic acid(HA)microneedles(MNs)as a vehicle to aid the transdermal delivery of therapeutic agent,a model TCM called shikonin for the treatment of hypertrophic scars.Here,shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration,making its dosage controllable during the fabrication process.The therapeutic effect of the shikonin MNs was studied in vira using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction.Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes(i.e.,TGFβ1,FAP-αand COL1 A1).Furthermore,we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.展开更多
基金supported by the National Natural Science Foundation of China(No.82222066)the National Key Research and Development Program of China(No.2022YFC2304104)。
文摘The complex skin structure and insufficient intracellular entrapment limit the therapeutic effects of active substances,therefore appealing to a more effective transdermal drug delivery system design.Herein,a hyaluronic acid(HA)modified steareth-2-based niosomes(HA-nio)with satisfactory deformability and targeting properties was designed for ergothioneine(EGT)(EGT@HA-nio)against ultraviolet(UV)-induced skin damage.The unique composition allows EGT@HA-nio to exhibit high mechanical softness,making it deformable to pass through the stratum corneum by the intercellular space without rupture.For further intracellular delivery,HA modification enables EGT to target human dermal cells(HDFs)with increased distribution in mitochondria without the restriction of specific EGT transporter-organic cation transporter1(OCTN-1).Benefiting from the above properties,an adequate amount of EGT in the active form was accumulated in the desired cellular sites,alleviating UV-radiation-induced reactive oxygen species(ROS)generation,inflammatory factor release,DNA damage,and mitochondrial dysfunction.The in vivo experimental results show that EGT@HA-nio could significantly decrease collagen degradation,restore epidermal thickness and morphology to healthy levels,and effectively prevent UV-induced skin damage.With the ability to penetrate biological barriers and deliver drugs,HA-nio may promote the development of inadequate drug penetration disease treatment including skin diseases,cancers,and bacterial infections.
基金supported by the National Natural Science Foundation of China(Nos.81872823,82073782,and 82241002)the Key R&D Plan of Ganjiang New District of Jiangxi(No.2023010).
文摘Candida albicans is one of the most common pathogens causing invasive fungal infections,with a mortality rate of up to 20%-50%.Amphotericin B(AmB),a biopharmaceutics classification system(BCS)IV drug,significantly inhibits Candida albicans.AmB is primarily administered via oral and intravenous infusion,but severe infusion adverse effects,nephrotoxicity,and potential hepatotoxicity limit its clinical application.Deep eutectic solvents(DESs),with excellent solubilization ability and skin permeability,are attractive for transdermal delivery.Herein,we used DESs to deliver AmB for antifungal therapy transdermally.We first prepared and characterized DESs with different stoichiometric ratios of choline(Ch)and geranate(Ge).DESs increased the solubility of AmB by a thousand-fold.In vitro and in vivo,skin permeation studies indicated that DES_(1:2)(Ch and Ge in 1:2 ratio)had the most outstanding penetration and delivered fluorescence dye to the dermis layer.Then,DES_(1:2)-AmB was prepared and in vitro antifungal tests demonstrated that DES_(1:2)-AmB had superior antifungal effects compared to AmB and DES_(1:2).Furthermore,DES_(1:2)-AmB was skin-irritating and biocompatible.In conclusion,DES-AmB provides a new and effective therapeutic solution for fungal infections.
基金The Key Direction Program of Chinese Academy of Sciences(Grant No.kjcx2-sw-h12-01)
文摘One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transdermal delivery of docetaxel （DTX）, a model drug for high molecular weight and poorly water-soluble drugs. Surfactant-ethanolic liposomes （SEL） were composed of phospholipids, ethanol, sodium cholate, DTX and PBS which were prepared by thin film dispersion method. The developed formulations were characterized by determining the vesicle shape and surface morphology, size and size distribution, entrapment efficiency and drug loading capacity. The effects of the developed formulations on the permeation of DTX across rat skin in vitro were investigated using the modified Franz diffusion cell under both occlusive and non-occlusive application condi- tions. The DTX SELs with optimum composition （phospholipid-surfactant, 85：15, w/w） provided a significantly higher steadystate amount of flux and cumulative permeation, compared to the tranditional liposomes, surfactant liposomes and ethanolic liposomes. The optimal SELs exhibited stable vesicle size, morphology and drug loading capacity. Our results indicated that SELs were promising carriers to enhance the transdermal delivery of DTX.
文摘Aim To study the influence of electric field direction on the in vitro enhanced transdermal delivery of caffeine by eleetroporation. Methods Using side-by-side compartment diffusion cells method and Ag-Ag/AgCl electrodes, the transport of caffeine through human cadaver skin by electroporation （exponentially decaying pulse, pulse voltage = 350 V, pulse frequency = 4 pulses· min^-1, capacity = 22 μF, pulse length = 7 ms, 25 pulses） with different electric field directions was carried out and compared with passive diffusion and iontophoresis （0.25 mA·cm^ - 2, lasted for 4 h）. Results （i） The cumulative quantity and flux of caffeine through human skin were increased significantly by eleetroporation or iontophoresis. （ii） The transport of caffeine by positive iontophoresis （ with electric field from donor to receptor compartment） was significantly greater than that by negative iontophoresis （with electric field from receptor to donor compartment）. （iii） The transport of caffeine by positive eleetroporation （with electric field from donor to receptor compartment） was similar to that by negative eleetroporation （with electric field from receptor to donor compartment）. （iv） The enhancing effect of positive iontophoresis on the transdermal delivery of caffeine was significantly greater than that of electroporation （positive or negative）. Conclusion Electric field direction significantly influences the enhancing effect of iontophoresis on the transdermal delivery of caffeine, but does not influence the enhancing effect of eleetroporation.
文摘Aim Liposomal fluconazole gel was prepared and its properties were studied. Methods The fluconazole liposomes were prepared by film dispersion method. Their shapes and sizes were observed by transmission electronic microscope and particle size analyzer, respectively. The skin permeation of liposomal gel was studied on rat skin by permeation cell. Results The entrapment efficiency of flueonazole liposomes was 47.68%. The fluconazole liposomes were oval or round in shape, and their average diameter was 250 ± 8 nm. The accumulative skin permeation of liposomal fluconazole gel （25.27%） was lower than that of non-liposomal fluconazole gel （36.72%）, but fluconazole retained in rat skin of liposomal gel （162 ± 15 μg·cm^-2） was higher than that of nonliposomal gel （48 ± 6μg·cm^-2）. Conclusion Liposomal fluconazole gel can significantly increase the deposited amounts of fluconazole in rat skin and it may be beneficial for topical use.
基金supported by the National Natural Science Foundation of China(No.51873194)the Natural Science Foundation of Zhejiang Province,China(No.LY18E030006).
文摘Injection therapy for diabetes has poor patient compliance,and the pain occurring at the site of subcutaneous injections causes significant inconvenience to diabetic patients.In this work,to demonstrate the benefits of an alternative drug delivery technique that overcomes these issues,methacrylated gelatin hydrogel-forming microneedles integrated with metformin were developed to adjust blood glucose levels in diabetic rats.Gelatin methacryloyl microneedles(GelMA-MNs)with different degrees of substitution were successfully prepared by a micro-molding method.The resultant GelMA-MNs exhibited excellent mechanical properties and moisture resistance.Metformin,an anti-diabetic drug,was further encapsulated into the GelMA-MNs,and its release rate could be controlled by the three-dimensional cross-linked network of microneedles,thereby exhibiting sustained drug release behaviors in vitro and implying a better therapeutic effect compared with that of subcutaneous injection in diabetic rats.The drug release period could be significantly prolonged by improving the cross-link density of GelMA-MNs.The results of hypoglycemic effect evaluation show that the application of GelMA-MNs for transdermal delivery in diabetic rats has promising benefits for diabetes treatment.
基金Supported by of the "863" Program of China(No 2003AA2Z347C)
文摘Microemulsion systems, composed of water, isopropyl myristate （IPM）, polyoxyethylene sorbitan trioleate （Tween 85 ）, and ethanol, were investigated as transdermal drug delivery vehicles for a lipophilic model drug（ meloxicam）. The purpose of this study was to investigate the physicochemieal properties of the tested microemulsion and to find the correlation between the physicoehemical properties and the skin permeation rate of the microemulsion. Pseudo-ternary phase diagram of the investigated system at a constant surfactant/cosurfactant mass ratio （ Km = 1 ： 1 ） was constructed by titration at 20℃, and the five fommlations were selected for further research in the o/w microemulsion domains. The values of electrical conductivity and viscosity showed that the selected systems were bicontinuous or non-spherical o/w microemulsion, and the electrical conductivity and viscosity were increased with increasing the content of water. These results suggest that the optimum formulation of microemulsion, containing 0. 375 meloxicam, 5% isopropyl myristate, 25% Tween 85. 25% ethanol, and water, showed the maximum permeation rate. It had a high electrical conductivity, small droplet size, and proper viscocity.
基金funded through the scholarship from the College of Health Sciences,University of Kwa Zulu Natal granted to the first author
文摘Objective: To report the influence of transdermal delivery of asiatic acid(AA) in Plasmodium berghei-infected Sprague Dawley rats on physicochemical changes, %parasitaemia and associated pathophysiology. Methods: A topical once-off AA(5, 10, and 20 mg/kg)- or chloroquine(CHQ)-pectin patch was applied on the shaven dorsal neck region of Plasmodium berghei-infected Sprague Dawley rats(90-120 g) on day 7 after infection. Eating and drinking habits, weight changes, malaria effects and %parasitaemia were compared among animal groups over 21 d. Results: AA-pectin patch application preserved food and water intake together with %weight gain. All animals developed stable parasitaemia(15%-20%) by day 7. AA doses suppressed parasitaemia significantly. AA 5 mg/kg patch was most effective. AA and CHQ displayed bimodal time-spaced peaks. CHQ patch had a longer time course to clear parasitaemia. Conclusions: AA influences bio-physicochemical changes and parasitaemia suppression in dose dependent manner. In comparison by dose administered, AA has much better efficacy than CHQ. AA may be a useful antimalarial. AA and CHQ displays bimodal peaks suggesting possible synergism if used in combination therapy.
基金supported by the National Natural Science Foundation of China(No.82072044)the Qing Lan Project of Jiangsu Province of China。
文摘Diabetic pressure ulcers(DPU)are non-healing due to vascular dysfunction and bacterial infection.Early intervention can delay ulcer progression,such as preventing the formation of full-thickness skin defects.Local administration of deferoxamine(DFO)at wound sites has been shown to promote neovascularization and enhance wound healing.However,since DPU skin wounds are not full-thickness defects and DFO is hydrophilic,enhancing its transdermal delivery is crucial for effective treatment.Photothermal ablation of stratum corneum,generated by copper sulfide nanoparticles(Cu S NPs)under near-infrared(NIR)light irradiation,is a promising method to improve transdermal drug delivery.Meanwhile,Cu S NPs-induced photothermal therapy offers excellent antibacterial performance.In this study,DFO and Cu S NPs were incorporated into a matrix metalloproteinase(MMPs)-sensitive hydrogel.This hydrogel promotes cell adhesion and is degraded by cell-secreted MMPs,a process crucial for the controlled release of encapsulated DFO and Cu S NPs.Under NIR irradiation,the stratum corneum is disrupted,facilitating transdermal DFO delivery and simultaneously eliminating infected bacteria.As a result,the essential requirements for DPU treatment,“facilitating transdermal DFO delivery,promoting angiogenesis,and inhibiting bacterial infection”,were achieved simultaneously.
基金the Thailand Research Fund through the Basic Research Grant(Grant No.5680016)the Faculty of Pharmacy,Silpakorn University,and Mr.Subhachai Saibour,the factory director and department manager at Bangkok Lab and Cosmetics Co.,Ltd.,for facilities and financial support.
文摘This study aimed to evaluate the patient-friendly methods that are used in the delivery of hydrophilic macromolecules into deep skin layers,in particular,the combination of microneedles patch(MNs patch)and low-frequency sonophoresis(SN).The hydrophilic macromolecule drug fluorescein isothiocyanate(FITC)-dextrans(FD-4:MW 4.4 kDa)was used as the model drug in our experimental design.In this study,excised porcine skin was used to investigate and optimize the key parameters that determine effective MNs-and SNfacilitated FD-4 delivery.In vitro skin permeation experiments revealed that the combination of MNs patch with SN had a superior enhancing effect of skin permeation for FD-4 compared to MNs alone,SN alone or untreated skin,respectively.The optimal parameters for the combination of MNs and SN included the following:10 N insertion force of MNs,4 W/cm^(2)SN intensity,6 mm radiation diameter of the SN probe,2 min application time,and the continuous mode duty cycle of SN.In addition,vertical sections of skin,clearly observed under a confocal microscope,confirmed that the combination of MNs and SN enhanced permeation of FD-4 into the deep skin layers.These studies suggest that the combination of MNs and SN techniques could have great potential in the delivery of hydrophilic macromolecules into deep skin.
基金supported by the NINGBO Medical & Health Leading Academic Discipline Project (No. 2022-ZF02)Ningbo Major Research and Development Plan Project (No.2023Z207)。
文摘Atopic dermatitis(AD) is a chronic inflammatory skin condition. Natural products have gained traction in AD treatment due to their accessibility, low toxicity, and favorable pharmacological properties. However, their application is primarily constrained by poor solubility, instability, and limited permeability. The transdermal drug delivery system(TDDS) offers potential solutions for transdermal delivery, enhanced penetration, improved efficacy, and reduced toxicity of natural drugs, aligning with the requirements of modern AD treatment. This review examines the application of hydrogels, microneedles(MNs), liposomes, nanoemulsions, and other TDDS-carrying natural products in AD treatment, with a primary focus on their effects on penetration and accumulation in the skin. The aim is to provide valuable insights into the treatment of AD and other dermatological conditions.
基金The project supported by National Natural Science Foundation of China(81573613,81373896)the Major Program for the Fundamental Research of Shanghai Committee of Science and Technology(14JC1491300)Open Fund of State Key Laboratory of Natural Medicines(SKLNMKF201612)
文摘The traditional Chinese medicine tripterygium glycosides(TPG)is used clinically to treat some Rheumatism,Eczema,immunosuppression and tumor,with the activities of hypnosis,antipyretic,analgesic,antiinflammatory,allergy and antitumor.However TPG has low water solubility and low skin permeability,so its clinical use is limited.Transdermal delivery systems can provide a controlled drug release rate that can keep constant concentrations of drug in the plasma for up to multiple days,improved patient compliance,and the possibility ofreducing the rate and severity of side effects.In this study,a fast and sensitive technique skin-blood two sites synchronous microdialysis coupled with LC-MS was used to study the pharmacokinetic parameter of three different formulations(TPG nanoemulsion,TPG nanoemulsion based gels and TPG gel).Creating a multilayer model,use the model to simulate the three formulations dynamics in transdermal-drug delivery system.The experiment results showed that the TPG nanoemulsion,TPG nanoemulsion based gels can significantly raise the drug concentrations in skin more than that of TPG gels.The numerical simulation results indicating that TPG gel and TPG nanoemulsion are close to practical measurements,only in the concentration increase phase the numerical simulation result has some difference with the experimental results.TPG nanoemulsion based gels have significant difference with the experimental results,both in concentration increase stage and concentration decreasing stage,but its trend was same.The study shows that the skin-blood synchronous microdialysis technique provided a new method for the pharmacokinetics study of nanocarriers transdermal delivery systems.In addition,the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery system.
基金supported by the National Key R&D Program of China(No.2022YFB3203700)the National Natural Science Foundation of China(Nos.82072012 and 82102230)the 111 Project of China(No.B07014).
文摘Epinephrine is important for first aid and usually applied via injection,which is painful and problematic in operation,thereby making it difficult to self-delivery.In this study,a method to actively transdermal delivery of epinephrine is proposed based on incorporating microneedles with iontophoresis,and then a wearable device is fabricated for rapid and controllable self-delivery of epinephrine.The device consists of a hydrogel microneedle array,a conductive drug delivery hydrogel,iontophoresis electrodes,and an encapsulated cartridge with a spring and self-locking micro-mechanism.The microneedles create subcutaneous microchannels,allowing the epinephrine contained in the hydrogel to enter the body under the control of iontophoretic currents.The dosage and rate can be adjusted at different levels by pressing the button so that it can be used by different groups of people for rapid self-aid and recovery from fatigue.The device can be worn in advance if required.In-vitro tests showed that the transdermal delivery rate of the device was between 0.02642 and 0.1059 mg/h cm^(2).As a proof-of-concept application,in-vivo experiments showed that the device could reverse life-threatening shock reactions in a piglet model of hemorrhagic shock through the delivery of epinephrine.
基金the Non-profit Central Research Institute Fund of National Research Institute for Family Planning(2023GJZD01,2023GJZ04)CAMS Innovation Fund for Medical(No.2018-I2M-1-004).
文摘Endometrial injury and resulting female infertility pose significant clinical challenges due to the notable shortcomings of traditional treatments.Herein,we proposed a double network composite hydrogel,CSMA-RCZn-PNS,which forms a physical barrier on damaged tissue through photo-crosslinking while enabling sus-tained release of the active ingredient PNS.Based on this,we developed a combined strategy to enhance transdermal delivery efficiency using ultrasound cavitation.In vitro experiments demonstrated that CSMA-RC-Zn-PNS exhibits excellent biosafety,biodegradability,and promotes cell proliferation,migration,and tube forma-tion,along with antioxidant and antibacterial properties.In a rat endometrial injury model,the ultrasound cavitation effect was demonstrated to enhance transdermal delivery efficiency,and the ability of CSMA-RC-Zn-PNS to promote endometrial regeneration,anti-fibrosis and fertility restoration was verified.Overall,this strategy combining CSMA-RC-Zn-PNS hydrogel and ultrasound treatment shows promising applications in endometrial regeneration and female reproductive health.
文摘Transdermal drug delivery offers the benefits of first-pass metabolism avoidance,high bioavailability,a low dose,and high patient compliance.Ethosomes are lipid-based vesicles containing phospholipids,ethanol,and water that enhance drug penetration by overcoming the barrier of the skin.Ethosomes can encapsulate lipophilic as well as hydrophilic drugs to increase their efficacy.Zingerone(ZNE)is a major component found in gingerroot and has potent antidiabetic,antioxidant,and antispasmodic activities.ZNE has low solubility in aqueous media,which leads to low oral bioavailability.ZNE-loaded ethosomes were prepared via the cold method.The ethosomes were optimized by a 3-level and 2-factor full factorial design.The independent variables selected were ethanol(%)and soy lecithin(%).The dependent variables selected were flux(μg/cm^(2)/h)and entrapment efficiency(%).The optimized formulation was evaluated for size,polydispersity index,zeta potential,entrapment efficiency,in vitro drug release,and ex vivo skin drug permeation.The optimized formulation had an average vesicle size of 77.12±1.89 nm,a polydispersity index of 0.350±0.013,a zeta potential of -56.9±1.25 mV,an entrapment efficiency of 75.83%±1.53%,in vitro drug release of 85.97%±1.92%(after 24 h),and ex vivo skin drug permeation of 78.52%±1.62%.The optimized formulation was converted to a gel formulation and characterized for in vitro parameters.The percent permeation of ZNE through rat skin(ex vivo)from the ethosomal gel was greater(73.12%±1.76%)than that from the conventional gel(38.17%±1.82%).This study reveals the substantial potential of ZNE-loaded ethosomes for transdermal delivery and for use in the management of systemic diseases.
文摘The global burden of cancer, a progressive disease with complex etiology, continues to rise. With an estimated 1.5 million new diagnoses each year, including nearly 350 000 cases of highly aggressive melanoma, the need for improved therapeutic strategies is paramount. The World Health Organization(WHO) and the International Labour Organization have established a clear link between occupational exposure to solar ultraviolet radiation(UVR) and increased risk of non-melanoma skin cancer(NMSC). While age, skin tone, and cumulative UVR exposure are recognized risk factors, current treatment modalities, including chemotherapy and surgery, often exhibit limited efficacy and significant side effects. This underscores the urgent need for novel therapeutic approaches that enable targeted drug delivery, enhanced tumor penetration, and reduced systemic toxicity. Transferosomes-based drug delivery systems have emerged as a promising avenue for achieving these goals, with vesicular systems offering a particularly attractive strategy for transdermal skin cancer therapy. This review focuses on transferosomes and transethosomes as such vesicular systems, highlighting recent advances in their application for targeted skin cancer treatment.
基金support from the National Research Foundation of Korea(RS-2024-00352352)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)+1 种基金support of the industry-academia cooperation research of Mimetics Co.,Ltdsupported by theSungKyunKwanUniversity and the BK21 FOUR(Graduate School Innovation)funded by the Ministry of Education(MOE,Korea)and National Research Foundation of Korea(NRF)。
文摘Transdermal drug delivery(TDD)systems have evolved,with skin electronics emerging as a technology capable of enabling efficient drug administration.However,conventional skin electronics often rely on rigid materials and expensive fabrication processes,limiting flexibility and skin-adhesion.In this study,we developed cellulose nanofiber(CNFs)-based adhesive electronics by integrating a three-dimensional octopus-inspired architecture(OIA)and a conductive layer.The OIA imprinted on CNFs enhanced adhesion by leveraging the synergistic effect of its adhesive structure and the ability to remain stable even after absorbing active ingredient solutions.Unlike conventional fiber-based TDD platforms,the optimized CNFs-OIA retains its architecture,enabling suction-based adhesion to improve skin attachment.To further enhance the TDD efficiency,we integrated a conductive layer into the CNFs-OIA.This conductive interface generates microcurrents that reduce the electrical resistance of the stratum corneum and facilitates the ionization of active ingredients,thereby improving skin penetration.
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.
文摘Aim To prepare triamcinolone-acetonide-acetate (TAA)-loaded solid lipidnanoparticles (SLN) carbomer gel with tripalmitin glyceride (TPG), and investigate theircharacteristics and transdermal drug delivery. Methods SLN suspension was prepared by high-pressurehomogenization technique, and then mixed with carbomer gel matrix to get SLN gel. The morphology,particle size with polydispersi-ty index (PI) and zeta potential were examined by atomic forcemicroscopy (AFM) and photon correlation spectroscopy (PCS). The entrapment efficiency, stability andin vitro drug release were also studied. The transdermal drug delivery through porcine ear skin wasevaluated using modified Franz diffusion cells. Results The SLN had a spherical shape with theaverage size of (95.5 - 186.2) nm, the zeta potential of (-26.3- -15.7) mV and the entrapmentefficiency of 67.4%-90.3% for different TAA encapsulated compounds. TAA-SLN carbomer gel had goodstability, the release profile in vitro fitted Higuchi equation. In comparison with conventionalhydrogels, TAA-SLN carbomer gel resulted in higher drug permeation amount and drug deposition withinporcine ear skin after 24 h penetration experiment. Conclusion TAA-SLN carbomer gel is preparedwith stable physicochemical properties. The release profile and improved drug permeation into skinmake it be a promising vehicle for transdermal drug delivery.
基金support from Singapore Agency for Science,Technology and Research(A*STAR)Science and Engineering Research Council Additive Manufacturing for Biological Materials(AMBM)program(A18A8b0059,Singapore)City University of Hong Kong(#9610472,China)+1 种基金General Research Fund(GRF)from University Grant Committee of Hong Kong(UGC)Research Grant Council(RGC)(#9042951,China)NSFC/RGC Joint Research Scheme(N_City U118/20,China)
文摘Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to lose efficacy over prolonged applications.Traditional Chinese medicine(TCM)offers as a promising candidate to treat pathological scars.A large number of TCMs have been studied to show anti-scarring effect,however,the natural barrier of the skin impedes their penetration,lowering its therapeutic efficacy.Herein,we reported the use of dissolvable hyaluronic acid(HA)microneedles(MNs)as a vehicle to aid the transdermal delivery of therapeutic agent,a model TCM called shikonin for the treatment of hypertrophic scars.Here,shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration,making its dosage controllable during the fabrication process.The therapeutic effect of the shikonin MNs was studied in vira using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction.Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes(i.e.,TGFβ1,FAP-αand COL1 A1).Furthermore,we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.
