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
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
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, f...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.展开更多
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 act...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.展开更多
Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits...Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.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
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 wi...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.展开更多
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 a...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.展开更多
Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used gi...Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used ginger oil,a phytochemical with potential therapeutic properties,to prepare ginger oil patches.High-performance liquid chromatography(HPLC)was used to quantify the main active component of ginger oil,6-gingerol.Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers,including their type and concentration.Subsequently,the ginger oil patches were optimized and subjected to content determination and property evaluations.A PTSD mouse model was established using the foot-shock method.The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections,behavioral tests,and the evaluation of biomarkers such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),brain-derived neurotrophic factor(BDNF),and melatonin(MT).Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels.Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day,addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy.Conclusions: Ginger oil can be prepared as a transdermal drug patch that meets these requirements,and the bioavailability of the prepared patch is better than that of oral administration.It can improve PTSD with good patient compliance and ease of administration.Therefore,it is a promising therapeutic formulation for the treatment of PTSD.展开更多
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 b...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.展开更多
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 penetra...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.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
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
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 hypode...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.展开更多
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, ampli...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.展开更多
Electroporation creates aqueous pathways by short high-voltage pulses resulting in a transient perme- abilization of stratum corneum and an increase in the transdermal delivery rate.However the aqueous pathways will r...Electroporation creates aqueous pathways by short high-voltage pulses resulting in a transient perme- abilization of stratum corneum and an increase in the transdermal delivery rate.However the aqueous pathways will reseal after pulsing,which leads to the rapid drop of transdermal flux.In the present study,the surfactants were added to the donor solution to hinder the shrinkage and resealing of the electropore,and to prolong the lifetime of the aqueous pathways with the consideration that the surfactants could reduce the surface energy of the electropore. These effects of surfactants were demonstrated by the dynamic electrical resistance of the skin and the fluorescent imaging of the local transport regions.Piroxicam(PIX)was transported percutaneously in the presence of surfac- tants in vitro.Owing to the longer lifetime of aqueous pathways,together with the promotion of PIX availability at the barrier exterior and the improvement in the partition of PIX into the aqueous pathways,the presence of surfac- tants led to a remarkable increase in the transdermal delivery rate during electroporation and a significant growth of the accumulative transdermal amount of PIX.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
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 extr...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.展开更多
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 National Natural Science Foundation of China(Nos.52277150,51977096,12005076 and 52130701)the National Key Research and Development Program of China(No.2021YFE0114700)。
文摘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.
基金funded by the National Natural Science Foundation of China(82273881 and 82304386)Guangdong Basic and Applied Basic Research Foundation(2022A1515110476)+1 种基金the Open Fund of Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology(GDKL202214)SUMC Scientiffc Research Initiation Grant(510858046 and 510858056).
文摘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.
文摘Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.
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supported by Zhejiang Provincial Natural Science Foundation of China under Grant No.LYY21H300001Zhejiang Medical and Health Science and Technology project under Grant No.2021KY906Hangzhou Medical Key Discipline Construction Project under Grant No.[2021]21–39
文摘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.
基金Supported by the Grant from the Agriculture Technologies R & D Program of Shanxi Province, China(No. 2007032013).
文摘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.
基金supported by the National Natural Scientific Foundation(82172186)Beijing Natural Scientific Foundation(L222126).
文摘Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used ginger oil,a phytochemical with potential therapeutic properties,to prepare ginger oil patches.High-performance liquid chromatography(HPLC)was used to quantify the main active component of ginger oil,6-gingerol.Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers,including their type and concentration.Subsequently,the ginger oil patches were optimized and subjected to content determination and property evaluations.A PTSD mouse model was established using the foot-shock method.The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections,behavioral tests,and the evaluation of biomarkers such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),brain-derived neurotrophic factor(BDNF),and melatonin(MT).Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels.Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day,addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy.Conclusions: Ginger oil can be prepared as a transdermal drug patch that meets these requirements,and the bioavailability of the prepared patch is better than that of oral administration.It can improve PTSD with good patient compliance and ease of administration.Therefore,it is a promising therapeutic formulation for the treatment of PTSD.
基金Natural Science Foundation of Shanghai,China(No.12ZR1400300)the Innovation Foundation of Donghua University,China(No.EG2015067)+1 种基金the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry,China“111 Project”Biomedical Textile Materials Science and Technology,China(No.B07024)
文摘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.
基金Yunnan Provincial Science and Technology Department University Joint Project:Effect and mechanism of microneedle transdermal administration of Periplaneta Americana extract on aging skin of mice(202001BA070001-214).
文摘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.
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.
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financial support from the National Natural Science Foundation of China (32071342 and 31922042)Guangdong Special Support Program (2019TQ05Y209)the Fundamental Research Funds for the Central Universities (19ykzd31)。
文摘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.
基金Project partially supported by the National Natural Science Foundation of China(Grant Nos.81127901,81227004,81473692,81673995,11374155,11574156,11274170,11274176,11474001,11474161,11474166,and 11674173)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK2011812)+1 种基金the Fundamental Research Funds for the Central Universitiesthe National High-Tech Research and Development Program of China(Grant No.2012AA022702)
文摘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.
基金Supported by the National Natural Science Foundation of China (No.20376038) and Tsinghua Basic Research Foundation (No.JCqn2005033).
文摘Electroporation creates aqueous pathways by short high-voltage pulses resulting in a transient perme- abilization of stratum corneum and an increase in the transdermal delivery rate.However the aqueous pathways will reseal after pulsing,which leads to the rapid drop of transdermal flux.In the present study,the surfactants were added to the donor solution to hinder the shrinkage and resealing of the electropore,and to prolong the lifetime of the aqueous pathways with the consideration that the surfactants could reduce the surface energy of the electropore. These effects of surfactants were demonstrated by the dynamic electrical resistance of the skin and the fluorescent imaging of the local transport regions.Piroxicam(PIX)was transported percutaneously in the presence of surfac- tants in vitro.Owing to the longer lifetime of aqueous pathways,together with the promotion of PIX availability at the barrier exterior and the improvement in the partition of PIX into the aqueous pathways,the presence of surfac- tants led to a remarkable increase in the transdermal delivery rate during electroporation and a significant growth of the accumulative transdermal amount of PIX.
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The study was financed by the Financing Scheme of Arising Interdisciplinary Subject of TCM in Shanghai,China(No.Shxxjcxk201709)the TCM Genre Program of Shanghai Health Bureau of China(No.ZY(2018-2020)-CCCX1006)the Shanghai Sports Bureau Project of China(Nos.20J020 and 21J013).
文摘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.