Development of Phospholipids Vesicular Nanocarrier for Topical Delivery of Tea Tree Oil in Management of Atopic Dermatitis Using BALB/c Mice Model

This work aims to develop and evaluate the efficacy of tea tree oil (TTO) ethosomal cream with improved deposition in skin layers for treatment of atopic dermatitis (AD). Ethosomes of TTO are developed using phosphatidylcholine (2% and 3% w/v) and ethanol (20%, 30%, and 40% w/v). Ethosomes are evaluated for percent entrapment efficiency (%EE), vesicle size, zeta potential, and in vitro drug diffusion. Ethosomal creams with optimized ethosomal dispersion are developed and evaluated for physicochemical parameters, thermal stability, ex vivo permeation, skin retention, and in vitro cytotoxicity using HaCat skin cell lines in comparison to conventional creams of TTO. In vivo investigations of optimized creams are performed using BALB/c mice model. The %EE, vesicle size, and zeta potential for optimized ethosomes are found to be 76.19 ± 3.26%, 333.6 nm, and –35.3 mV, respectively. Ethosomal creams showed higher deposition in the epidermis and dermis. The optimized creams are non-cytotoxic to HaCat cell lines. The creams significantly reduce the inflammatory response by decreasing the clinical score and infiltration of white blood cells, eosinophils, and IgE antibodies. Overall efficacy of ethosomal cream is higher than conventional cream. In conclusion, optimized ethosomal cream of TTO shows good efficacy for treatment of AD. Practical applications : The method used for the formulation of ethosomes is simple and can be easily scaled up on the industrial level. The loading of TTO within ethosomes can increase the efficiency by enhanced drug deposition in the epidermis and might also improve its stability against oxidative degradation. Topical ethosomal cream of TTO can improve patient compliance by avoidance of adverse effects linked with corticosteroids and could be a possible complementary or alternative therapy in management of AD.     

Elastic vesicles as topical/transdermal drug delivery systems

Skin acts a major target as well as a principle barrier for topical/transdermal drug delivery. Despite the many advantages of this system, the major obstacle is the low diffusion rate of drugs across the stratum corneum. Several methods have been assessed to increase the permeation rate of drugs temporarily. One simple and convenient approach is application of drugs in formulation with elastic vesicles or skin enhancers. Elastic vesicles are classified with phospholipid (Transfersomes((R)) and ethosomes) and detergent-based types. Elastic vesicles were more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. Their effectiveness strongly depends on their physicochemical properties: composition, duration and application volume, and entrapment efficiency and application methods. This review focuses on the effect of elastic liposomes for enhancing the drug penetration and defines the action mechanism of penetration into deeper skin.     

Lipid-Based Nanosystems as a Tool to Overcome Skin Barrier

Skin may be affected by many disorders that can be treated by topical applications of drugs on the action site. With the advent of nanotechnologies, new efficient delivery systems have been developed. Particularly, lipid-based nanosystems such as liposomes, ethosomes, transferosomes, solid lipid nanoparticles, nanostructured lipid carriers, cubosomes, and monoolein aqueous dispersions have been proposed for cutaneous application, reaching in some cases the market or clinical trials. This review aims to provide an overview of the different lipid-based nanosystems, focusing on their use for topical application. Particularly, biocompatible nanosystems able to dissolve lipophilic compounds and to control the release of carried drug, possibly reducing side effects, are described. Notably, the rationale to topically administer antioxidant molecules by lipid nanocarriers is described. Indeed, the structural similarity between the nanosystem lipid matrix and the skin lipids allows the achievement of a transdermal effect. Surely, more research is required to better understand the mechanism of interaction between lipid-based nanosystems and skin. However, this attempt to summarize and highlight the possibilities offered by lipid-based nanosystems could help the scientific community to take advantage of the benefits derived from this kind of nanosystem.     

盐酸布替萘芬醇质体凝胶的制备与性质

摘 要：实验目的旨在制备盐酸布替萘芬醇质体并考察其性质,并与市售的布替萘芬软膏进行对比。利用乙醇注入均质法制备布替萘芬醇质体,利用正交试验优化处方。运用马尔文粒度仪对其粒径和电位进行测试,利用透析法测包封率,TEM检测存在其形态,用Franz扩散池对离体大鼠皮肤的透过能力和与布替萘芬软膏的透过能力进行对比。结果表明：优选的处方,乙醇用量40%,大豆卵磷脂用量5%,胆固醇0.25%,布替萘芬的用量1%;所得醇质体的平均粒径在253.9（±6）nm,平均电位在-33.4（±6）mV,包封率为34.06%;透过24h后,布替萘芬醇质体透过量占总量的11.8%,而布替萘芬软膏透过量占总量的0.6%,醇质体能显著的提高布替萘芬的经皮透过量。     

Design by optimization and comparative evaluation of vesicular gels of etodolac for transdermal delivery

Aim of the present study was to design vesicular gels of etodolac loaded liposomes and ethosomes for effective transdermal delivery. The physicochemical properties of vesicular gels were compared with 45% v/v ethanolic etodolac solution and commercial product (PROXYM®). The liposomes were prepared by film hydration technique whereas ethosomes were prepared by cold method respectively. Both the systems were characterized for various physicochemical properties. The size range of liposomes shows 186?nm–363?nm whereas for ethosomes 170?nm–261?nm respectively. The zeta potential of optimized liposomes and ethosomes was found to be ?36.5?mV and ?48.3?mV, respectively. The highest %EE of liposomes and ethosomes shows 71.5% and 78.5%, respectively. The permeation of liposomes shows in the range of 67.50%–86.06% whereas ethosomes shows 52.30%–99.49%, respectively. The optimization was done by 3² experimental design. The optimized vesicular dispersions were subjected to gel preparation using carbopol 940 NF. The prepared liposomal gel (ETO-LG) and ethosomal gel (ETO-EG) were optimized and characterized. The vesicular gels showed desirable results compared to other test formulations.     

醇质体的研究进展

目的介绍醇质体的制备方法、质量评价手段以及体内外透皮吸收的研究。方法以近年来国内外相关文献为依据,进行归纳总结。结果醇质体是一种稳定的透皮载体,流动性及变形性强,有较高的包封率,能显著增强药物对皮肤的渗透性,使药物能够传递到皮肤深层,甚至透过皮肤。结论作为经皮给药的载体,醇质体有良好的应用前景和开发价值。     

神经酰胺修饰醇质体的制备与表征

为了提高醇质体的稳定性，作者采用神经酰胺Ⅲ（ceramide III，Cer3） 修饰醇质体，首先考察了Cer3质量浓度对醇质体稳定性的影响，后将视黄醇棕榈酸酯（retinyl palmitate，RP） 作为脂溶性活性物载入Cer3醇质体，研究了RP-Cer3醇质体的稳定性、稳定机制及体外释放性能。结果显示，当Cer3质量浓度为1 mg/mL时，Cer3醇质体的稳定性最好。RP-Cer3醇质体的RP质量浓度为2 mg/mL时，粒径为（68.4±1.1） nm，室温储存120 d，外观和粒径均无明显变化。X射线衍射和全反射傅里叶红外光谱表明RP被很好地包载于醇质体中，同时，红外光谱图也说明了RP与醇质体存在氢键相互作用。研究表明，Cer3的加入会降低醇质体流动性从而提高其稳定性，且RP-Cer3醇质体具有较好的体外释放性能。