Asiatic acid-pectin hydrogel matrix patch transdermal delivery system influences parasitaemia suppression and inflammation reduction in P. berghei murine malaria infected Sprague-Dawley rats

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.

Characteristics and pharmacokinetics of tripterygium glycosides nano-carries transdermal delivery systems:skin-blood synchronous microdialysis and numerical simulation

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.

The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery

Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss(TEWL), molecular structure of the stratum corneum(SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields,charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.

Ionic liquids as the effective technology for enhancing transdermal drug delivery: Design principles, roles, mechanisms, and future challenges

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.

Physicochemical Properties and Evaluation of Microemulsion Systems for Transdermal Delivery of Meloxicam

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.

Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Investigation of Microemulsion System for Transdermal Drug Delivery of Amphotericin B

In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B（AmB）, microemulsion vehicles composed of isopropyl myristate（IPM）, Tween 80, isopropyl alcohol and water for transdermal delivery of AraB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conductivities（σ）. The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into microemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature（PIT） of the emulsifier obtains the maximum drug content（2.96 mg/mL）. The pH value of the system could be adjusted to pH〉8.5 or pH〈5.2, in this range AraB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1：1, O/SC 1：9（mass ratio of oil phase to surfactant/cosurfactant blend）, water content 64.6%, drug content （2.93±0.08） mg/mL, showed the maximum permeation rate （3.255 ±0.64） μg·cm^-2.h^-1 which is stable for a long time.

Ethosomes-Silk Fibroin/Polyvinyl Alcohol Composite Hydrogel Transdermal Drug Delivery System : Preparation and Characterization

One key of constructing ideal transdermal drug delivery system(TDDS)is enhancing the percutaneous rate of drugs without sacrificing compatibility.Ethosomes(Eths)have excellent transdermal performance as well as good biocompatibility,and thus been widely used as drug carrier.Hydrogel has good 3-dimensional mesh structure which is convenience for drugs release and storage.In this study,Eths were introduced into silk fibroin(SF)/polyvinyl alcohol(PVA)composite hydrogel to construct a novel TDDS through a green process.The Ethsomes(Eths)-SF/PVA composite hydrogel TDDS showed good mechanical properties(stress:(0.236±0.032)MPa;strain:(65.74±2.45)%).Also,skin fibroblasts can grow and proliferate well on this TDDS,indicating that this material has a good cytocompatibility.Furthermore,with doxorubicin hydrochloride(Dox)as a model drug loaded in ethosomes,in vitro studies showed that this TDDS was able to transdermally release Dox efficiently.Our data suggested this novel system had a good potential for application in TDD,though further evaluative study still needed to carry out.

Research progress on the application of microneedle transdermal drug delivery system in dermatology

Transdermal drug delivery systems(TDDs)have the advantages on good local targeting,controlled and sustainable drug delivery.Hoewever,the stratum corneum,as the main skin barrier,severely limits the transdermal penetration of drugs and reduces bioavailability,which also limits their application.Microneedles(MNS)penetrate the stratum corneum and create several reversible microchannels in a minimally invasive manner to significantly improve the penetration of therapeutic agents,and are considered a milestone for effective transdermal drug delivery.As an emerging drug delivery modality,microneedle transdermal drug delivery systems have the advantages of being minimally invasive,safe,efficient,economical and convenient.In addition to the extensive research on microneedles for improving transdermal drug delivery,there is a growing interest in using them to manage and treat dermatological conditions.Being the largest organ in the human body,the skin acts as a barrier between the body and the external environment,while having an immense influence on appearance and self-confidence.Indeed,there is now a considerable body of evidence on how dermatological conditions can lead to psychological problems and a reduced quality of life.The utilisation of microneedle transdermal drug delivery systems for the management and treatment of dermatological conditions is of great therapeutic and commercial value.The principleof microneedle transdermal drug delivery systems and the progress of its clinical application in dermatology are reviewed here.

Fabrication of gelatin methacryloyl hydrogel microneedles for transdermal delivery of metformin in diabetic rats

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.

Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

Transdermal drug delivery （TDD） can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow-green fluorescent nanoparticles and high molecular weight hyaluronic acid （HA） in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers （e.g., their penetration depth and concentration） could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents （UCAs）. When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 p.m. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 p.m, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications （e.g., nanoparticle drug carriers, transdermal patches and cosmetics）, protocols and methods presented in this paper are potentially useful.

Transdermal delivery of fluorescein isothiocyanate-dextrans using the combination of microneedles and low-frequency sonophoresis

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.

Polymeric microneedle-mediated sustained release systems: Design strategies and promising applications for drug delivery

Parenteral sustained release drug formulations, acting as preferable platforms for longterm exposure therapy, have been wildly used in clinical practice. However, most of these delivery systems must be given by hypodermic injection. Therefore, issues including needle-phobic, needle-stick injuries and inappropriate reuse of needles would hamper the further applications of these delivery platforms. Microneedles (MNs) as a potential alternative system for hypodermic needles can benefit from minimally invasive and self-administration. Recently, polymeric microneedle-mediated sustained release systems (MN@SRS) have opened up a new way for treatment of many diseases. Here, we reviewed the recent researches in MN@SRS for transdermal delivery, and summed up its typical design strategies and applications in various diseases therapy, particularly focusing on the applications in contraception, infection, cancer, diabetes, and subcutaneous disease. An overview of the present clinical translation difficulties and future outlook of MN@SRS was also provided.

Systematic Review and Meta-Analysis on the Effect of Transdermal Preparations of Sinomenium Acutum on Rheumatoid Arthritis

Objective:We evaluated the efficacy and safety of transdermal preparations of Sinomenium acutum(SA)for rheumatoid arthritis(RA).Methods:Randomized controlled trials(RCTs)of SA transdermal preparations for RA were extracted from relevant databases and screened in accordance with the inclusion criteria.The Cochrane System Evaluation Manual(version 5.1.0)was used to assess the quality of the included trials.We used the Cochrane Review Manager(version 5.4)to conduct the meta-analysis.Results:Six trials comprising 436 patients(220 patients in the treatment group and 216 patients in the control group)were analyzed.The meta-analysis indicated that SA transdermal preparations in combination with disease-modifying antirheumatic drugs(DMARDs)enhanced the overall effect(odds ratio[OR]3.97,95%confidence interval[CI][2.25,7.00],P<0.00001),decreased visual analogue scale(VAS)results(mean difference[MD]-0.64,95%CI[-1.20,-0.09],P=0.02),decreased laboratory indexes including the erythrocyte sedimentation rate(ESR)(MD-4.36,95%CI[-5.63,-3.08],P<0.00001)and C-reactive protein(CRP)(MD-3.6,95%CI[-3.99,-3.21,P<0.00001]),and decreased the Disease Activity Score-28(DAS28)(MD-0.41,95%CI[-0.78,-0.03],P=0.03).The results suggest that combination therapy did not shorten the duration of morning stiffness(DMS;standardized MD[SMD]-6.13,95%CI[-17.33,5.06],P=0.28)or reduce rheumatoid factor(RF)laboratory indexes(SMD-0.85;95%CI[-2.19,0.49],P=0.21).Only one study reported adverse reactions,and thus,it was difficult to determine whether adverse drug reactions in the combination therapy group were significantly different from those in the control group.Conclusion:We found that SA transdermal preparations combined with DMARDs may have greater clinical efficacy than DMARDs for RA.More well-designed and high-quality RCTs are required to verify the findings and determine whether transder-mal preparations cause fewer adverse events.

Applications and recent advances in transdermal drug delivery systems for the treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic,systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate.Several drugs have been used for the treatment of rheumatoid arthritis,but their use is limited by suboptimal bioavailability,serious adverse effects,and nonnegligible first-pass effects.In contrast,transdermal drug delivery systems(TDDSs)can avoid these drawbacks and improve patient compliance,making them a promising option for the treatment of rheumatoid arthritis(RA).Of course,TDDSs also face unique challenges,as the physiological barrier of the skin makes drug delivery somewhat limited.To overcome this barrier and maximize drug delivery efficiency,TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology,and different generations of TDDSs have been derived,which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery.In this review,we summarize the different generations of transdermal drug delivery systems,the corresponding transdermal strategies,and their applications in the treatment of RA.

Transdermal permeation of Zanthoxylum bungeanum essential oil on TCM components with different lipophilicity

Objective:To investigate the percutaneous penetration enhancement effect of essential oil from Zanthoxylum bungeanum Maxim.(Z.bungeanum oil)on active components in externally-applied traditional Chinese medicines.Methods:Five model drugs,geniposide,puerarin,ferulic acid,tetramethylpyrazine,and osthole,were chosen based on their lipophilicity and tested using in vitro transdermal permeation studies consisting of Franz diffusion cells and full thickness rat abdominal skin.Scanning electron microscopy was employed to observe the morphological changes of rat skin tissue after treatment with Z.bungeanum oil.The molecular interactions between the oil and the polar head groups in stratum corneum(SC)lipids were monitored using molecular dynamic simulation,and the SC/vehicle partition coefficients and saturation solubilities of the selected model drugs treated with and without the oil were also determined to ascertain its mechanisms of action.Results:As oil concentration increased,the log ERflow trended toward a negative linear relationship with the lipophilicity of drugs.After treatment with Z.bungeanum oil,a mild lifting up and wrinkle on the SC surface were observed,and appeared to become more pronounced as oil concentration increased.There was no significant difference between the control and the Z.bungeanum oil at different concentrations in terms of saturation solubility of GP,while saturation solubilities of the 4 other drugs gradually increased as oil concentration increased.The oxygen-containing constituents in Z.bungeanum oil,such as terpinen-4-ol and 1,8-cineole,which accounted for 57.95%of total oil,could form stable hydrogen bonds with the polar head group of ceramide 3.Conclusion:Z.bungeanum oil facilitated transdermal permeation of drugs with different lipophilicity,including the extremely hydrophilic and lipophilic drugs,whereas it exhibited greater enhancement activity for strongly hydrophilic drugs.The mechanisms of transdermal permeation enhancement by the oil could be explained with SC/vehicle partition coefficient,saturation solubility,and the interactions with SC lipids.

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch

Chronic pain lasting more than 3 mo,or even several years can lead to disability.Treating chronic pain safely and effectively is a critical challenge faced by clinicians.Because administration of analgesics through oral,intravenous or intramuscular routes is not satisfactory,research toward percutaneous delivery has gained interest.The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area.It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery,which reduces the dose frequency and side effects.If not required,then the patch can be removed from the skin immediately.The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979.From then on,the transdermal patch has been widely used to treat many diseases.To date,no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery.The pain branch of the Chinese Medical Association,after meeting and discussing with experts and based on clinical evidence,developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.

Efficacy and mechanism of methyl salicylate in the enhancement of skin delivery of herbal medicines

Objective: To elucidate the molecular mechanism(s) by which methyl salicylate enhances the skin delivery of herbal ingredients with diverse lipophilicity.Methods: The toxicity of methyl salicylate on skin cell lines was evaluated using the MTT assay. The Franz diffusion cell method was used to measure the permeability enhancing activities of methyl salicylate for five herbal ingredients with a range of lipophilicities. The interaction between methyl salicylate and the stratum corneum(SC) was observed by using an infrared spectroscopy technique. Moreover, the solubilities and SC-vehicle partition coefficient were determined to monitor the impact of methyl salicylate on the drug thermodynamic activities and partition into the SC layer, respectively.Results: Compared with azone(1-dodecylazacycloheptan-2-one), methyl salicylate showed lower toxicity to skin cells in terms of the IC50 values. The in vitro skin permeation studies showed that methyl salicylate could greatly improve the cumulative amounts or steady state flux of the selected model drugs with the exception of osthole, which indicated that methyl salicylate was prone to promote the skin delivery of hydrophilic drugs. The Fourier transform infrared spectroscopy studies revealed that methyl salicylate mainly interacted with SC lipids, leading to the disruption of the orderly arrangement of the SC.In addition, methyl salicylate had no obvious effect on the drug thermodynamic activity and partition into the SC.Conclusion: Methyl salicylate could effectively promote the skin delivery of relatively hydrophilic ingredients in externally used traditional Chinese medicines(TCM) without obvious cytotoxicity.

Progress in transdermal drug delivery systems for cancer therapy

Transdermal drug delivery is an appealing option except for oral and hypodermic administration.With the advancement of skin penetration strategies,various anticancer therapeutics ranging from liphilic small-molecule drugs to hydrophilic biomacromolecules,can be administered transdermally,offering an optional regimen to treat skin cancers.In addition,the activation of the skin immune systems can also assist the treatment of distal sites.Current approaches on enhancing the transdermal delivery efficacy of anticancer drugs are summarized in this review.We also survey recent advances in micro-and nanotechnology-based transdermal formulations for cancer treatment,such as chemotherapy,gene therapy,immunotherapy,phototherapy and combination therapy.New penetration enhancers,materials,formulations and their hypothesized mechanisms for transdermal delivery are highlighted.Advantages and limitations regarding the state-of-the-art transdermal delivery technologies,as well as future perspective are also discussed.

Wearable patches for transdermal drug delivery

Transdermal drug delivery systems(TDDs) avoid gastrointestinal degradation and hepatic first-pass metabolism, providing good drug bioavailability and patient compliance. One emerging type of TDDs is the wearable patch worn on the skin surface to deliver medication through the skin. They can generally be grouped into passive and active types, depending on the properties of materials,design principles and integrated devices. This review describes the latest advancement in the development of wearable patches, focusing on the integration of stimulus-responsive materials and electronics.This development is deemed to provide a dosage, temporal, and spatial control of therapeutics delivery.