变形脂质体作为促进咖啡因渗透通过人体皮肤的增强剂：Franz 扩散池试验。

Deformable liposomes as enhancer of caffeine penetration through human skin in a Franz diffusion cell test.

机构信息

Therapeutics Research Centre, Translational Research Institute, Diamantina Institute, University of Queensland, 37 Kent Street, Woolloongabba, Qld., 4072, Australia.

Departamento de Ciências Farmacêuticas, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Rua São Nicolau, 210, prédio de vidro, Diadema, SP, CEP 09913-030, Brazil.

出版信息

Int J Cosmet Sci. 2021 Feb;43(1):1-10. doi: 10.1111/ics.12659. Epub 2020 Oct 2.

DOI:10.1111/ics.12659

PMID:32866296

Abstract

OBJECTIVE

The permeation of hydrophilic molecules through the skin is still a challenge due to the barrier posed by stratum corneum, the outermost layer of the skin. Liposomes have frequently been used as carriers for different types of drugs and may also function as permeation enhancers. Propylene glycol has also been used as an edge activator in liposomes to increase the permeation. The aim of this work was to prepare liposomes containing an edge activator and loaded with caffeine to evaluate the potential of caffeine reaching the deeper layers in the skin.

METHODS

The formulations were prepared by a top-down process using high-pressure homogenization at 200 00 psi for 10 min. They were characterized by size, polydispersity index (PI), zeta potential (ZP), pH, caffeine content and encapsulation efficiency (EE%) on preparation (time zero) and after 30 days. Cytotoxicity of blank and loaded liposomes was assessed by MTT proliferation assay with a normal keratinocyte cell line (HaCaT). In vitro permeation tests were performed with human skin in Franz cells over 24 h, and caffeine concentration was determined in the skin surface, stratum corneum, dermo-epidermal fraction and receptor medium by HPLC.

RESULTS

The caffeine liposomes with (DL-Caf) or without propylene glycol (CL-Caf) showed, respectively, mean size 94.5 and 95.4 nm, PI 0.48 and 0.42, ZP + 1.3 and + 18.1 mV and caffeine content of 78.57 and 80.13%. IC values of caffeine in DL-Caf (3.59 v/v %) and CL-Caf (3.65 v/v %) were not significantly different from conventional blank liposome (3.27 v/v %). The DL-Caf formulation presented the best capability to enhance the caffeine permeation through the skin, resulting 1.94-folds higher than caffeine solution. Furthermore, the caffeine flux from DL-Caf was 1.56- and 3.05-folds higher than caffeine solution and CL-Caf, respectively. On the other hand, CL-Caf showed the lowest caffeine penetration revealing the importance of edge activator to aid hydrophilic drug penetration to all skin layers.

CONCLUSION

The DL-Caf formulation tested was able to improve the permeation of caffeine through the stratum corneum and dermo-epidermal layers, suggesting that this delivery system may be effective for deep skin delivery of hydrophilic drugs.

摘要

目的

由于角质层是皮肤的最外层，亲水分子的渗透仍然是一个挑战。脂质体经常被用作各种药物的载体，也可以作为渗透增强剂。丙二醇也被用作脂质体的边缘活性剂，以增加渗透。本工作的目的是制备含有边缘活性剂并负载咖啡因的脂质体，以评估咖啡因渗透到皮肤深层的潜力。

方法

通过在 200000 psi 下高压匀质 10 分钟，采用自上而下的方法制备配方。在制备时（零时）和 30 天后，通过大小、多分散指数（PI）、Zeta 电位（ZP）、pH 值、咖啡因含量和包封效率（EE%）对其进行了表征。采用 MTT 增殖试验评估空白和负载脂质体对正常角质形成细胞系（HaCaT）的细胞毒性。采用 Franz 细胞在 24 小时内进行体外渗透试验，通过 HPLC 测定皮肤表面、角质层、真皮表皮层和受体介质中的咖啡因浓度。

结果

分别含有丙二醇（DL-Caf）和不含有丙二醇（CL-Caf）的咖啡因脂质体的平均粒径为 94.5nm 和 95.4nm，PI 为 0.48 和 0.42，ZP 分别为+1.3mV 和+18.1mV，咖啡因含量分别为 78.57%和 80.13%。DL-Caf（3.59v/v%）和 CL-Caf（3.65v/v%）中的咖啡因 IC 值与常规空白脂质体（3.27v/v%）无显著差异。DL-Caf 制剂具有增强咖啡因通过皮肤渗透的最佳能力，其咖啡因渗透量是咖啡因溶液的 1.94 倍。此外，DL-Caf 的咖啡因通量分别是咖啡因溶液和 CL-Caf 的 1.56 倍和 3.05 倍。另一方面，CL-Caf 显示出最低的咖啡因渗透率，这表明边缘活性剂对于帮助亲水性药物渗透到所有皮肤层非常重要。