Recent Progress in Transdermal Nanocarriers and Their Surface Modifications

Transdermal drug delivery system (TDDS) is an attractive method for drug delivery with convenient application, less first-pass effect, and fewer systemic side effects. Among all generations of TDDS, transdermal nanocarriers show the greatest clinical potential because of their non-invasive properties and high drug delivery efficiency. However, it is still difficult to design optimal transdermal nanocarriers to overcome the skin barrier, control drug release, and achieve targeting. Hence, surface modification becomes a promising strategy to optimize and functionalize the transdermal nanocarriers with enhanced penetration efficiency, controlled drug release profile, and targeting drug delivery. Therefore, this review summarizes the developed transdermal nanocarriers with their transdermal mechanism, and focuses on the surface modification strategies via their different functions.     

Improvement in bioavailability of transdermally applied flurbiprofen using tulsi (Ocimum sanctum) and turpentine oil

Penetration enhancing potential of tulsi and turpentine oil on transdermal delivery of flurbiprofen, a potent non-steroidal anti-inflammatory agent, was investigated. The transdermal permeation rate of flurbiprofen across the rat abdominal skin from binary solvent mixture composition of propylene glycol (PG):isopropyl alcohol (IPA) (30:70%, v/v) was 98.88 microg/cm(2)/h, significantly higher than other binary solvent mixtures. The corresponding steady state plasma concentration, 0.71 microg/ml, was much lower than required steady state plasma concentration of 3-5 microg/ml. Hence influence of tulsi and turpentine oil in the optimized binary solvent mixture along with the increased drug load on the flurbiprofen permeation was evaluated. The magnitude of the flux enhancement factor with turpentine oil and tulsi oil was 2.4 and 2.0 respectively at 5% (v/v) concentration beyond which there was no significant increase in the flux. Addition of 2% (w/v) hydroxypropyl methylcellulose (HPMC), as a thickening agent, resulted in desired consistency for the fabrication of patch with insignificant effect on permeation rate of flurbiprofen. The reservoir type of transdermal patch formulation, fabricated by encapsulating the flurbiprofen reservoir solution within a shallow compartment moulded from polyester backing film and microporous ethyl vinyl acetate membrane, did not modulate the skin permeation of flurbiprofen through rat skin in case of turpentine formulations whereas flux of formulations with tulsi oil was significantly altered. The influence of penetration enhancer and solvents on the anatomical structure of the rat skin was studied. Enhancement properties exhibited by turpentine oil and tulsi oil in optimized binary solvent mixture were superior as compared to solvent treated and normal control groups with negligible skin irritation. The fabricated transdermal patches were found to be stable. The bioavailability of flurbiprofen with reference to orally administered flurbiprofen in albino rats was found to increase by 2.97, 3.80 and 5.56 times with transdermal patch formulation without enhancer, tulsi and turpentine oil formulations, respectively. The results were confirmed by pharmacodynamic studies in rat edema inflammation model.     

Film‐ and ointment‐based delivery systems for the transdermal delivery of TNP‐470

Pathological angiogenesis, the process of new blood vessel formation, is responsible for a broad range of neovascular‐related systemic diseases. One of the first antiangiogenic compounds tested in clinical trials against cancer was TNP‐470. Despite promising activity the injectable drug showed poor plasma stability and caused adverse side effects in high doses lead to termination of the trials. In our current work, we introduce the development of a transdermal delivery systems for controlled release of TNP‐470. Such formulation can potentially reduce toxicity due to controlled continuous dosing and improve stability by avoiding gastrointestinal first pass metabolism. Although transdermal delivery is a very challenging route for drug administration due to the low permeability of the skin, here we present a successful development of two different drug delivery systems, film and ointment for dermal application of TNP‐470. Chitosan film had high loading capacity of up to 50% w/w of TNP‐470 compared with 10% maximum loading in hydrocarbon ointment. A detailed step‐by‐step development of TNP‐470 films, from the initial solvent screening to final optimized formulation, is presented. Ex vivo skin permeation studies demonstrated a superior release of the drug from the film formulation compared with the ointment. Furthermore, histological test of the skin confirmed ointment safety showing no evidence of skin tissues damage. Our results present novel, promising, controlled release drug delivery systems with improved stability, efficacy, and safety profile of TNP‐470 via transdermal route.     

Nano-formulations for transdermal drug delivery: A review

The different applications of nano-formulations (vesicles or nanoparticles and nanoemulsions) have been widely studied. Here, the classification, characteristics, transdermal mechanism, and application of the most popular nano-formulations in transdermal drug delivery system are reviewed.     

Oleogel Formulations for the Topical Delivery of Betulin and Lupeol in Skin Injuries—Preparation,Physicochemical Characterization,and Pharmaco-Toxicological Evaluation

The skin integrity is essential due to its pivotal role as a biological barrier against external noxious factors. Pentacyclic triterpenes stand as valuable plant-derived natural compounds in the treatment of skin injuries due to their anti-inflammatory, antioxidant, antimicrobial, and healing properties. Consequently, the primary aim of the current investigation was the development as well as the physicochemical and pharmaco-toxicological characterization of betulin- and lupeol-based oleogels (Bet OG and Lup OG) for topical application in skin injuries. The results revealed suitable pH as well as organoleptic, rheological, and textural properties. The penetration and permeation of Bet and Lup oleogels through porcine ear skin as well as the retention of both oleogels in the skin were demonstrated through ex vivo studies. In vitro, Bet OG and Lup OG showed good biocompatibility on HaCaT human immortalized cells. Moreover, Bet OG exerted a potent wound-healing property by stimulating the migration of the HaCaT cells. The in ovo results demonstrated the non-irritative potential of the developed formulations. Additionally, the undertaken in vivo investigation indicated a positive effect of oleogels treatment on skin parameters by increasing skin hydration and decreasing erythema. In conclusion, oleogel formulations are ideal for the local delivery of betulin and lupeol in skin disorders.     

ZnO Nanoparticles of Rubia cordifolia Extract Formulation Developed and Optimized with QbD Application,Considering Ex Vivo Skin Permeation,Antimicrobial and Antioxidant Properties

The objective of the current research is to develop ZnO-Manjistha extract (ZnO-MJE) nanoparticles (NPs) and to investigate their transdermal delivery as well as antimicrobial and antioxidant activity. The optimized formulation was further evaluated based on different parameters. The ZnO-MJE-NPs were prepared by mixing 10 mM ZnSO₄·7H₂O and 0.8% w/v NaOH in distilled water. To the above, a solution of 10 mL MJE (10 mg) in 50 mL of zinc sulfate was added. Box–Behnken design (Design-Expert software 12.0.1.0) was used for the optimization of ZnO-MJE-NP formulations. The ZnO-MJE-NPs were evaluated for their physicochemical characterization, in vitro release activity, ex vivo permeation across rat skin, antimicrobial activity using sterilized agar media, and antioxidant activity by the DPPH free radical method. The optimized ZnO-MJE-NP formulation (F13) showed a particle size of 257.1 ± 0.76 nm, PDI value of 0.289 ± 0.003, and entrapment efficiency of 79 ± 0.33%. Drug release kinetic models showed that the formulation followed the Korsmeyer–Peppas model with a drug release of 34.50 ± 2.56 at pH 7.4 in 24 h. In ex vivo studies ZnO-MJE-NPs-opt permeation was 63.26%. The antibacterial activity was found to be enhanced in ZnO-MJE-NPs-opt and antioxidant activity was found to be highest (93.14 ± 4.05%) at 100 µg/mL concentrations. The ZnO-MJE-NPs-opt formulation showed prolonged release of the MJE and intensified permeation. Moreover, the formulation was found to show significantly (p < 0.05) better antimicrobial and antioxidant activity as compared to conventional suspension formulations.     

Photobinding of ketoprofen in vitro and ex vivo

Ketoprofen (KP), a non-steroidal anti-inflammatory drug of the 2-aryl propionic class, has been shown to produce photoallergic side effects as well as cutaneous photosensitizing properties that induce other phototoxic effects. In the present study we investigated photobinding of ketoprofen to both human serum albumin (HSA), a model protein, and to ex vivo pig skin and its photodegradation. Results demonstrate that photoadduct formation and photodegradation progressively increased with irradiation time where they reach a maximum. Maximum photobinding to the viable layer of the epidermis was about 7-8% of the initial radiolabelled KP added, in the region of 15-30 min UV irradiation. These results were comparable to in vitro results that were seen with photobinding of KP to HSA; in this case, the quantity of covalently bound material was approximately 10% of the initial, after a maximum of 18 min irradiation. It was found by HPLC analysis that the KP decrease is accompanied by an increase of the corresponding photoproduct, decarboxylated ketoprofen (DKP). The yield of DKP reaches a maximum at around 15 min. DKP appears to play an important role in vitro and ex vivo, being the major photoproduct and responsible for the photobinding process. Using micro-autoradiographical techniques we investigated the penetration and distribution of ketoprofen in ex vivo pig skin in greater detail. It was apparent that percutaneous absorption was taking place and that most of the ketoprofen was predominately localised in fibroblasts in the papillary dermis. No other specific localisation within the skin architecture was identified. Although there were differences in the quantities of bound ketoprofen within the different layers of the skin, these levels did not appear to correlate with irradiation time.     

Fabrication of Alginate-Based O/W Nanoemulsions for Transdermal Drug Delivery of Lidocaine: Influence of the Oil Phase and Surfactant

Transdermal drug delivery of lidocaine is a good choice for local anesthetic delivery. Microemulsions have shown great effectiveness for the transdermal transport of lidocaine. Oil-in-water nanoemulsions are particularly suitable for encapsulation of lipophilic molecules because of their ability to form stable and transparent delivery systems with good skin permeation. However, fabrication of nanoemulsions containing lidocaine to provide an extended local anesthetic effect is challenging. Hence, the aim of this study was to address this issue by employing alginate-based o/w nanocarriers using nanoemulsion template that is prepared by combined approaches of ultrasound and phase inversion temperature (PIT). In this study, the influence of system composition such as oil type, oil and surfactant concentration on the particle size, in vitro release and skin permeation of lidocaine nanoemulsions was investigated. Structural characterization of lidocaine nanoemulsions as a function of water dilution was done using DSC. Nanoemulsions with small droplet diameters (d < 150 nm) were obtained as demonstrated by dynamic light scattering (DLS) and cryo-TEM. These nanoemulsions were also able to release 90% of their content within 24-h through PDMS and pig skin and able to the drug release over a 48-h. This extended-release profile is highly favorable in transdermal drug delivery and shows the great potential of this nanoemulsion as delivery system.     

Evaluation of the predicted time-concentration profile of serum tulobuterol in human after transdermal application

We proposed an in vitro/in vivo/in silico method for evaluating the clinical performance of matrix type transdermal therapeutic systems (TTSs). This method is based on the following four approaches: (1) drug release experiment, (2) in vitro penetration experiment using excised hairless mouse skin, (3) clinical pharmacokinetic study, and (4) mathematical model for evaluating the pharmacokinetic profile. The tulobuterol TTS was used as an example of a matrix type TTS in this study. The drug diffusion coefficient in the matrix device was calculated from the result of the release experiment. The drug diffusion coefficient and the partition coefficient in the skin were calculated from the results of in vitro skin penetration experiments where hairless mice and rats were used. Those parameters were used as substitutes of human. Further, these parameters were used for solving the governing partial differential equation on skin penetration. The time profiles of the serum concentration in human after applying the tulobuterol TTS were predicted and compared with the clinical data. The predicted profiles obtained from the data of hairless mice reproduced the influence of drug depletion adequately and well agreed with the clinical data, while those from the data of rats differed clearly in the initial rise. This method is useful for prediction of pharmacokinetic profiles of TTSs.     

Solubility enhancement of ibuprofen using tri-ureasil-PPO hybrid: structural,cytotoxic, and drug release investigation

Herein, we used tri-ureasil organic–inorganic hybrid material (tU5000) in order to enhance the solubility of nonsteroidal anti-inflammatory drugs and fine tuning the drug delivery profile. For the first time, we used tU5000 as a film-forming agent in order to provide an alternative vehicle for transdermal drug delivery systems which the cell viability of practically 100 % for the highest and the lowest tested concentrations of pure tU5000 indicated that the material was not cytotoxic. The physicochemical properties of the tU5000 drug carrier and drug-loaded hybrids were systematically studied using powder X-ray diffraction, differential scanning calorimetry, small-angle X-ray scattering, and Fourier-transform infrared spectroscopy. The structural changes of tU5000 as well as the relationships between the drug content and in vitro drug release behaviors were investigated. The results showed that the ibu molecules were homogeneously distributed in the tU5000 xerogels contributing to fine-tuning the drug delivery profile. Considering the ability to incorporated high drug content, simple and mild preparation procedure by one-pot sol–gel route, high stability of the materials, sustained-release property, this class of hybrid based on polymers and inorganic compounds may have potential applications in the design of pharmaceutical formulation as ophthalmic (contact lenses), transdermal (patches) and implantable (soft tissue) drug delivery systems.     

Dissolvable Carboxymethylcellulose Microneedles for Noninvasive and Rapid Administration of Diclofenac Sodium

The aim of this study is to prepare dissolvable biopolymeric microneedle (MN) patches composed solely of sodium carboxymethylcellulose (CMC), a water-soluble cellulose derivative with good film-forming ability, by micromolding technology for the transdermal delivery of diclofenac sodium salt (DCF). The MNs with ≈456 µm in height displayed adequate morphology, thermal stability up to 200 °C, and the required mechanical strength for skin insertion (>0.15 N needle⁻¹). Experiments in ex vivo abdominal human skin demonstrate the insertion capability of the CMC_DCF MNs up to 401 µm in depth. The dissolution of the patches in saline buffer results in a maximum cumulative release of 98% of diclofenac after 40 min, and insertion in a skin simulant reveals that all MNs completely dissolve within 10 min. Moreover, the MN patches are noncytotoxic toward human keratinocytes. These results suggest that the MN patches produced with CMC are promising biopolymeric systems for the rapid administration of DCF in a minimally invasive manner.     

Electron beam processed transdermal delivery system for administration of an anti-anginal agent

Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak^®1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate–EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.     

Transdermal permeation of tetracaine hydrochloride by lecithin microemulsion: in vivo

In vivo transdermal permeation of tetracaine hydrochloride encapsulated in lecithin water-in-oil and oil-in-water microemulsion was studied. The effect of the composition of the lecithin microemulsion on analgesic response of tetracaine hydrochloride was evaluated on Wistar rats by tail flick method. To find out the toxicity of lecithin/n-propanol/isopropyl myristate/water/tetracaine hydrochloride microemulsion histopathological and irritation response were measured in Swiss mice. Time course studies were also conducted for the biochemical response of microemulsion by measuring catalase, glutathione and lipid peroxidation levels of the treated mice skin. The analgesic response was found to be dependent on the drug concentration and composition of the systems. The histopathological, irritation and biochemical findings reveal that lecithin/n-propanol/isopropyl myristate/water/tetracaine hydrochloride microemulsion is a safe carrier for transdermal drug delivery systems. Confocal laser scanning microscopy observation indicated that sweat gland and hair follicle also provided the path for transdermal permeation of lecithin/n-propanol/isopropyl myristate/water microemulsion.     

Acrylate terpolymer in fabrication of medicated skin patches

An acrylate based pressure sensitive adhesive (PSA) was synthesized to design a drug‐in‐adhesive (DIA) type transdermal therapeutic system (TTS) for nitroglycerin used in the treatment of angina pectoris. 2‐Ethylhexyl acrylate (EHA), methyl methacrylate (MMA) and acrylic acid (AA) were used to synthesize the PSA by free radical solution polymerization. The effects of reaction time, reaction temperature, initiator concentration and solvent on polymerization were studied. The synthesized terpolymer was characterized by ¹H‐NMR, FT‐IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and also evaluated for intrinsic viscosity, refractive index, peel strength, moisture uptake and skin irritation potential. The PSA was used to develop DIA type patches of nitroglycerin. The patches were cast using solvent evaporation technique and dried at controlled temperature. The patches were evaluated for thickness uniformity, weight variation, peel strength and moisture pick‐up. The percent drug content and in vitro drug release was determined by high pressure liquid chromatography (HPLC) method. On the basis of in vitro release profile, patches were selected for in vitro skin permeation studies. The developed formulation TP‐1 (K = 24.892 mcg/cm²/hr) followed zero‐order rate kinetics and showed better skin permeation rate in comparison to the marketed TTS (MTTS) (K = 17.413 mcg/cm²/hr). TP‐1 was subjected to stability testing for a period of 1 year according to ICH guidelines. The patches were found to be stable and an expiry date of 2 years was predicted with storage at 25 °C or below. Copyright © 2001 John Wiley & Sons, Ltd.     

Design of original bioactive formulations based on sugar-surfactant/non-steroidal anti-inflammatory catanionic self-assemblies: a new way of dermal drug delivery

A new kind of catanionic assembly was developed that associates a sugar-based surfactant with a non-steroidal anti-inflammatory drug (NSAID). Three different assemblies using indomethacin, ibuprofen and ketoprofen as NSAIDs were easily obtained in water by an acid-base reaction. These assemblies formed new amphiphilic entities because of electrostatic and hydrophobic effects in water and led to the spontaneous formation of vesicles. These catanionic vesicles were then tested as potential NSAID delivery systems for dermatological application. The anti-inflammatory activity was evaluated in vivo, and this study clearly showed an improved therapeutic effect for NSAIDs that were formulated as catanionic vesicles. These vesicles ensured a slower diffusion of the NSAID through the skin. This release probably increased the time of retention of the NSAID in the targeted strata of the skin. Thus, the present study suggests that this catanionic bioactive formulation could be a promising dermal delivery system for NSAIDs in the course of skin inflammation treatment.     

External control of drug release and penetration. VI. Enhancing effect of ultrasound on the transdermal absorption of indomethacin from an ointment in rats.

The effect of an ultrasound (1 MHz) on transdermal absorption of indomethacin from an ointment was studied in rats. Ultrasound energy was supplied for between 5 and 20 min at a range of intensities (0.25, 0.5, 0.75, and 1 W cm-2), energy levels commonly used for therapeutic purposes. For evaluating skin penetration of indomethacin, the change of plasma concentration was measured. The pronounced effect of ultrasound on the transdermal absorption of indomethacin was observed at all ultrasound energy levels studied. The intensity and the time of application were found to play an important role in the transdermal phonophoretic delivery system of indomethacin; 0.75 W cm-2 appeared to be the most effective intensity in improving the transdermal absorption of indomethacin, while the 10 min ultrasound treatment was the most effective. Although the highest penetration was observed at an intensity of 0.75 W cm-2, 0.5 W cm-2 was preferred because intensities of less than 0.5 W cm-2 of ultrasound for 10 min did not result in any significant skin temperature rise nor did it have any destructive effect on rat skin. Progressively more skin damage was noted as the intensity and the time of application of ultrasound increased. When used at a proper intensity and time of application, ultrasound appears to be a safe technique for enhancing the passage of various drug molecules through human skin.     

Evaluation of nanoherbal gel for anti-warts activity

In the present experimental investigation a novel nanoherbal gel containing iron nanoparticles and extract from Cuscuta reflexa was used as a drug. Synthesized nanoherbal increased the drug solubility and penetration in the skin and is useful as a novel delivery system for better anti-warts activity. The experimental work includes preformulation studies of drug (Cuscuta reflexa) which include organoleptic properties, identification and solubility studies. Spectroscopy characterization was performed for identification of drug. The iron nanoparticles were evaluated for their characteristic such as appearance, viscosity and odor. Various formulations F1–F5 was prepared using different formulation variables based on experiment design. The result showed that the formulation F-5 provide the better release using 5.5 pH acetate buffer and at 37 °C temperature for anti-warts activity. The maximum drug release through synthesized nanoherbal gel was found to be 91.3%. Nanoherbal formulation was evaluated for physical appearance, pH, consistency, spreadibility and drug content. Stability study of formulation F5 was carried out for a period of 3 months to determine the percentage release and the results revealed that the formulation is stable under varied humidity and temperature condition and there was no major change in the amount of drug release during the storage condition, which reflected the stability of F5 formulation.     

A Novel Methacryloyl Chitosan Hydrogel Microneedles Patch with Sustainable Drug Release Property for Effective Treatment of Psoriasis

Psoriasis is a chronic and recurrent skin disease that often requires long-term treatment, and topical transdermal drug delivery can reduce systemic side effects. However, it is still a challenge in efficient transdermal drug delivery for psoriasis treatment due to low penetration efficiency of most drugs and the abnormal skin conditions of psoriasis patients. Here, a safe and effective methacryloyl chitosan hydrogel microneedles (CSMA hMNs) patch is developed and served as a sustained drug release platform for the treatment of psoriasis. By systematically optimizing the CSMA preparation, CSMA hMNs with excellent morphological characteristics and strong mechanical properties (0.7 N needle⁻¹) are prepared with a concentration of only 3% (w/v) CSMA. As a proof-of-concept, methotrexate (MTX) and nicotinamide (NIC) are loaded into CSMA hMNs patch, which can produce a sustained drug release of 80% within 24 h in vitro. In vivo experiments demonstrated that the CSMA hMNs patch can effectively inhibit the skin thickening and spleen enlargement of psoriatic mice and has a good biosafety profile at sufficient therapeutic doses. This study provides a new idea for the preparation of hMN systems using modified CS or other biocompatible materials and offers an effective therapeutic option for psoriasis treatment.     

Preparation of curcumin-loaded liposomes and evaluation of their skin permeation and pharmacodynamics

This study aimed to investigate the in vitro skin permeation and in vivo antineoplastic effect of curcumin by using liposomes as the transdermal drug-delivery system. Soybean phospholipids (SPC), egg yolk phospholipids (EPC), and hydrogenated soybean phospholipids (HSPC) were selected for the preparation of different kinds of phospholipids composed of curcumin-loaded liposomes: C-SPC-L (curcumin-loaded SPC liposomes), C-EPC-L (curcumin-loaded EPC liposomes), and C-HSPC-L (curcumin-loaded HSPC liposomes). The physical properties of different lipsomes were investigated as follows: photon correlation spectroscopy revealed that the average particle sizes of the three types of curcumin-loaded liposomes were 82.37 ± 2.19 nm (C-SPC-L), 83.13 ± 4.89 nm (C-EPC-L), and 92.42 ± 4.56 nm (C-HSPC-L), respectively. The encapsulation efficiency values were found to be 82.32 ± 3.91%, 81.59 ± 2.38%, and 80.77 ± 4.12%, respectively. An in vitro skin penetration study indicated that C-SPC-L most significantly promoted drug permeation and deposition followed by C-EPC-L, C-HSPC-L, and curcumin solution. Moreover, C-SPC-L displayed the greatest ability of all loaded liposomes to inhibit the growth of B16BL6 melanoma cells. Therefore, the C-SPC-L were chosen for further pharmacodynamic evaluation. A significant effect on antimelanoma activity was observed with C-SPC-L, as compared to treatment with curcumin solution in vivo. These results suggest that C-SPC-L would be a promising transdermal carrier for curcumin in cancer treatment.     

Structure and Performance Modulation of Self-Adhesive SIS/C5 Electrospun Membranes for Transdermal Drug Delivery北大核心CSCD

Electrospun membranes are widely utilized to enhance the water vapor permeability and drug delivery performance of transdermal drug delivery patches. Due to the lack of adhesion property,however,most of them cannot closely contact with skin,which impedes the delivery of drugs to the skin,thus affecting the transdermal administration. C5 resin is used to endow poly（styrene isoprene styrene）（SIS）electrospun membranes with pressure-sensitive adhesion property. Investigation is performed on how to control the structure,adhesion properties and drug delivery performance of SIS/C5 electrospun membranes loaded with synthetic capsaicin via compositions,drugs and electrospinning conditions. The results demonstrate that the electrospun membrane with a SIS/C5 ratio of 2∶1 has excellent water vapor permeability（7. 17×10－3 g/（h·cm2）and adhesion properties（180（°）peel strength is 0. 2 kN/m,tack force is 0. 64 N/cm2 ,holding power is greater than 7 days）. The synthetic capsaicin has good compatibility with the SIS/C5 electrospun membranes,in which no drug crystallizes and the drug loading is beneficial to improve the water vapor permeability. As the drug loading is 8%,the tack force is 0. 6～0. 8 N/cm2 ,the 180（°）peel strength is 0. 2～0. 3 kN/m,the holding power is greater than 7 days,and no residue is left during peeling tests. In vitro drug release indicates that the drug has a behavior of sustained release with a 24-hour cumulative release rate of greater than 50% for all SIS/ C5 electrospun membranes,meeting the requirements of transdermal drug delivery patches. © 2022, Science Press (China). All rights reserved.