Application progress of parallel artificial membrane permeation assay model in drug permeability screening of transdermal drug delivery system / 中国药房

The traditional model Franz diffusion cell method has always been the “gold standard” for evaluating the permeability of transdermal drug delivery system （TDDS） drug. However， in the high throughput screening of a large number of drug molecules， it has the disadvantages of low efficiency， high cost， difficulty to obtain isolated skin，poor reliability and large workload. The emergence of parallel artificial membrane permeation assay （PAMPA） model provides reliable pre-prediction data for the evaluation of permeability of TDDS drug. PAMPA model has been widely used in the permeability screening research of TDDS drugs and their preparations such as analgesics， local anesthetics， antioxidants， antipyretics， analgesics and anti-inflammatory drugs， vitamins， cholinesterase inhibitors， active ingredients of natural products， and has the characteristics of high reliability， good selectivity， high efficiency， low cost and data stability. PAMPA model has greatly improved the high throughput screening efficiency of TDDS drug permeability. With the extensive application and gradual maturity of this model， it will become a new and effective evaluation method in addition to the traditional evaluation model.

Preparation of triptolide-loaded dissolving microneedles and its transdermal penetration / 中国中药杂志

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 μm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) μg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.

Fabrication of Non-Ionic Surfactant Vesicular Gel for Effective Treatment of Rheumatoid Arthritis.

Rheumatoid Arthritis (RA) is a chronic, inflammatory auto immune disorder with unknown aetiology. Though various efficacious treatment options are currently available to treat RA, failure to cure is unpredictable. Hence the present study aimed to evaluate Piroxicam (PC) loaded non-ionic surfactant vesicular carrier as transdermal patches. MethodsTransdermal patches of PC- niosomes were formulated by solvent casting method using different polymers. The prepared formulation was examined for physico - chemical and morphological characteristics and drug release studies were performed by Franz diffusion cell method. ResultsThe results of physico-chemical characterizations show that all formulations were with optimum range and morphological characterization shows that the prepared niosomes are spherical in shape. Drug release characteristic of all formulations was performed and the result exhibits that formulation TN4 (PC encapsulated niosomal gel transdermal patch) shows highest % drug release (95.13%) when compared to other formulation. The release data was fitted with release kinetics and results shows zero order with non Fickian diffusion mechanism. ConclusionsPC encapsulated vesicular carrier as transdermal patches is a promising drug delivery system to enhance the solubility of poorly soluble drugs. It also enhances the residence time of drug at absorption site. Hence this approach could be beneficial for the effective management of RA.

Improving Transdermal Drug Delivery System For Medroxyprogesterone Acetate By Olive Oil And Dimethylsulfoxide (DMSO) As Penetration Enhancers: In Vitro Penetration Study

Objective: Medroxyprogesterone Acetate (MPA) using a transdermal drug delivery system for contraception by passive diffusion is limited by the skin barrier properties. Penetration enhancers such as olive oil (fatty acid permeation enhancer) and DMSO (chemical enhancer) can be used. The objective of this study was to overcome MPA penetration problem by using olive oil and DMSO. Methods: An in vitro penetration study using the Franz diffusion cells was performed. The first penetration study used MPA in olive oil (O) and MPA in coconut oil (C) with the concentration 100 μg/ml to each sample and MPA suspension as a control with the same concentration. The second study used MPA in olive oil with the concentration 200.0 μg/ml (A), MPA in olive oil with 0.5% DMSO with the concentration 200.0 μg/ml (B), and MPA in olive oil with 1% DMSO with the concentration 200 μg/ml (C). Results: MPA penetration test for olive oil+0.5% DMSO had flux value 4.24±0.074 μg/cm2. hr and it was not significantly different (t-test, P>0.05) with olive oil+1% DMSO. While the MPA penetration test in only Olive oil had flux value 0.90±0.0087 μg/cm2. hr. Conclusion: This research concluded that olive oil and 0.5% DMSO could improve the penetration of MPA into skin membrane by 4.5 times more than olive oil alone.

Preparation of neurotoxin loaded dissolving microneedles and its transdermal penetration / 中草药

Objective: To prepare Naja atra neurotoxin (NT) loaded dissolving microneedles (DMNs-NT), and investigate the physicochemical properties and in vitro transdermal properties. Methods: DMNs-NT was prepared by a two-step centrifugation method. The ratio of CS and PVP K30, the water content of the matrix solution, and the backing layer material were optimized by the indexes of formability and mechanical strength of the microneedles and flexibility of the backing layer. The drug loading content was determined by HPLC, and the morphological characteristics were observed under an optical microscope, and the stability was also examined. Franz diffusion cell was used to investigate its in vitro skin permeation characteristics. Results: Through the single-factor exploration, we confirmed that the optimal prescription technique for DMNs-NT preparation was a 1:1 ratio of CS and PVP k30, a 5:4 ratio of matrix material and water, with CMC as the backing layer material. The DMNs-NT had a pyramidal shape with a smooth surface and a length of approximately 500 μm. The drug loading content of per tablet was (15.4 ± 0.5) μg. The drug was located in the upper part of the needle. DMNs-NT had good stability within 3 months. The results of in vitro skin permeation assay showed that the cumulative penetration of NT in DMNs-NT could reach 95.8% in 4 h, while NT solution barely penetrated the skin, which proved that it had a good promoting effect on NT transdermal delivery. Conclusion: In this study, DMNs-NT had good mechanical properties and good skin penetration, which realized the transdermal drug delivery of macromolecular drugs.

Progress of Electrospinning Drug-loaded Fibers and Application in Transdermal Drug Delivery System / 中国药学杂志

Electrospinning technology opens up a new method for the construction of drug delivery system. The unique fiber structures of drug-loaded electrospinning nanofibers with the characteristics of similar to the extracellular matrix,good air permeability and hygroscopicity are very suitable for transdermal drug delivery systems.In this paper, the definition, characteristics, matrix selection, preparation methods, drug-loaded forms and drug-released profiles of drug-loaded electrospinning nanofibers are summarized and analyzed. Meanwhile, the application of drug-loaded electrospinning nanofbiers in the transdermal drug delivery systems is analyzed. This review is to provide support for the further studies on electrospun nanofiber transdermal drug delivery system.

Microneedles: quick and easy delivery methods of vaccines

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route.

Preparation and evaluation of novel hydrogel of Bletilla striata polysaccharide / 中草药

Objective: To prepare the hydrogels using Bletilla striata polysaccharides (BSP) as groundmass and evaluate its properties. Methods: BSP were successfully extracted and characterized by Fourier Transform Infrared Spectrometer, thermogravimetric analysis, differential thermal analysis, and X-ray diffraction. The BSP was incorporated with Carbopol 940 to prepare hydrogels. Rheological behavior of the gels was investigated by rotational rheometer, skin permeation properties and bioactivities of BSP gels were evaluated by trans-epidermal water loss (TEWL) and blood coagulation examinations respectively using mice as model animals. Results: The BSP was pure with complete structure. The BSP gels showed the better viscoelasticity and physical strength from carbopol gel. The gels showed better skin permeation enhancement and hemostatic activity. Conclusion: This work demonstrates the skin permeation enhancement and plasma coagulation effects of BSP hydrogels, which show great potential in transdermal drug delivery system and wound dressing.

Preparation of transdermal drug delivery system of carbon nanotubes graft ginsenosides Rb1 and Rb2 nanoemulsion / 中成药

AIM To prepare the transdermal drug delivery system of carbon nanotubes graft ginsenosides Rb1 and Rb2 nanoemulsion.METHODS After 0.5％ carbon nanotubes' dispersion into the prepared nanoemulsion,the combination state was observed under transmission electron microscope.The skin irritation and transdermal mechanism of this drug delivery system were investigated.Then the UVA-damaged mouse skin model was established to evaluate the antioxidant activity.RESULTS Carbon nanotubes had strong adsorption to nanoemulsion,together with the formation of drug storage cavern in epidermis,thus increased the transdermal osmotic quantities of ginsenosides Rb1 and Rb2.The SOD activity in mouse skin tissue in the drug delivery system group was higher than that in the model group and the nanoemulsion group (P ＜0.01),and the MDA content was significantly decreased (P ＜ 0.01).CONCLUSION The transdermal drug delivery system of carbon nanotubes graft ginsenosides Rb1 and Rb2 nanoemulsion can make drugs play an antioxidant role because of its less irritation to skin and better skin permeability.

Formulation and evaluation of transdermal drug-delivery system of isosorbide dinitrate / Formulação e avaliação de sistema transdérmico droga-entrega de dinitrato de isossorbida

The purpose of this study was to develop a reservoir-type transdermal delivery system for isosorbide dinitrate (ISDN). The developed patch consisted of five layers from bottom to top, namely, a temporary liner, an adhesive layer, a rate-controlling membrane, a reservoir and a backing. The effects of chemical penetration enhancers, reservoir materials and rate-controlling membranes on the release behaviour of ISDN from the transdermal patch were studied, and the in vitro release of ISDN from the developed patch was studied and compared with the commercially available ISDN patch. The results showed that there was no significant difference in permeation rates between the developed reservoir-type patch and the commercially available ISDN patch (p> 0.05). Moreover, the cumulative release ratio of the commercially available ISDN patch in 48 h was up to 89.8%, whereas the developed patch was only 34.9%, which meant the sustained release time of the developed patch was much longer than the commercially available ISDN patch, and would promote the satisfaction of the patient...

O objetivo do presente estudo foi desenvolver um sistema de liberação transdérmico do tipo reservatório para o dinitrato de isossorbida (ISDN, abrevitura em Inglês). A formulação transdérmica desenvolvida constou de cinco camadas de baixo para cima, ou seja, um revestimento temporário, uma camada adesiva, uma membrana controladora da taxa de liberação, um reservatório e um reforço. Estudaram-se os efeitos dos potenciadores de penetração química, materiais do reservatório e membranas de controle da taxa de liberação no comportamento da formulação transdérmica de dinitrato de isossorbida. A liberação in vitro da formulação transdérmica de dinitrato de isossorbida desenvolvida foi estudada em comparação com a formulação de dinitrato de isossorbida disponível comercialmente. Os resultados mostraram que não existem diferenças significativa nas taxas de permeação entre o tipo de reservatório desenvolvido e o de dinitrato de isossorbida desenvolvido comercialmente (p>0,05). Ademais, a taxa de liberação cumulativa da formulação de dinitrato de isossorbida disponível comercialmente em 48 horas foi de até 89,8% e a da formulação desenvolvida, de apenas de 34,9%, o que provou que a liberação sustentada da formulação desenvolvida foi muito maior do que a de dinitrato de isossorbida desenvolvida comercialmente, o que promoveria a satisfação do paciente...

Research Progress of Penetration Enhancers / 中国中医药信息杂志

Penetration enhancers are substances to improve the rate or amount of transdermal permeation which is an important factor in transdermal drug delivery systems (TDDS). Recent researches have found that some of the new penetration enhancers have a higher penetration-effect, little irritation, fewer adverse reactions, and stable properties. In this article, domestic and foreign research reports on penetration enhancers have been collected and summarized. The research progress of penetration enhancers were reviewed, with a purpose to provide a reference for reasonable selection of penetration enhancers.

Progress in researches for cell-penetrating peptides as skin penetration enhancer / 中国药学杂志

OBJECTIVE: To review the progress in researches for cell-penetrating peptides as skin penetration enhancer.

Evaluation of Kollidon SR based Ketorolac Tromethamine Loaded Transdermal Film.

The present study concerns the development of polymeric films of Ketorolac tromethamine by solvent casting method to explore the possibilities of using kollidon SR as a transdermal drug delivery system. Ketorolac tromethamine was used as a model drug & incorporated in low doses. The films were prepared by using various amounts of Kollidon SR to prolong the drug release with localized action. Some films were also prepared containing certain percent of PEG-6000 along with the drug & polymer. The prepared polymeric films were evaluated for various parameters like weight uniformity, flatness, % elongation, surface pH, uniformity of drug content, in-vitro dissolution studies. The drug-polymer ratio was found to influence the drug release. The rate of drug release decreased with increased polymer concentration. About 10% increased in polymer concentration causes 50% decreased drug release. All the formulation followed Higuchian kinetics & the mechanism of release was diffusion mediated. When PEG-6000 was used as a channeling agent in this formulation drug release was increased accordingly but higher concentration of PEG-6000 results in decreasing release rate of drug because of increasing viscosity of the matrix channels.

Double-layer patch containing gestodene and ethinylestradiol :preparation and in vitro/in vivo characterization / 中国药科大学学报

Aim: To prepare a novel contraceptive patch containing gestodene(GEST) and ethinylestradiol(EE), and to study the in vitro characterization and in vivo contraceptive effect. Methods: Double-layer technique was applied to sustain steady 7-day permeation flux of drugs. Polariscope examination was carried out to observe the drug distribution behavior in the patch. Uniformity, adhesion, skin irritation, release and permeation tests were conducted to evaluate in vitro characterization. Anti-implantation and anti-fertility experiments were carried out to investigate its contraceptive effect. Results: The in vitro release profiles of both drugs were in accordance with Higuchi equation. The daily permeated amount of GEST per 10 cm2 patch was about 75 μg while the amount of EE was 30 μg.The in vitro transdermal permeation of both drugs from the patches displayed a zero-order process. Permeation rate constants were 0. 377 μg/(cm2·h) for GEST, and 0. 092 μg/(cm2· h) for EE, respec-tively. After transdermal administration, the embryonic number of the test groups was zero, and the uterus coefficients of those groups were significantly reduced compared with those of the control group (P < 0. 01). Conclusion: Double-layer transdermal drug delivery system(TDDS) could allow the steady 7-day permeation flux of drugs when the drug ratio between the immediate-release layer and the reservoir layer was 1:4. In vivo charac-terization demonstrated its contraceptive effects. The prepared novel patch might be a promising non-oral contra-ceptive preparation.

A new immune strategy:Transcutaneous immune / 中国药理学通报

Transcutaneous immunization(TCI),the topical application of antigen and adjuvant directly onto intact skin,which can safely and effectively elicit systemic and celluar immune responses in mice and humans against a variety of antigens,is a novel method of vaccine delivery.Not only the skin has evolved as a barrier to prevent external agents,including pathogens,from entering the body,but also it has a complex and efficient immune system,which includes Langerhans′ cells and dendritic cells.The skin is an attractive target for vaccine delivery.By targeting the body′s natural defense system,TCI attempts to produce an efficient immune response.All these results highlight the likelihood that TCI will play an important role in vaccine applications in the future.