Ascenso Andreia, Salgado Ana, Euletério Carla, Praça Fabíola Garcia, Bentley Maria Vitória Lopes Badra, Marques Helena C, Oliveira Helena, Santos Conceição, Simões Sandra
Instituto de Investigação do Medicamento (iMed.ULisboa), Universidade de Lisboa, Lisboa, Portugal.
Instituto de Investigação do Medicamento (iMed.ULisboa), Universidade de Lisboa, Lisboa, Portugal.
Eur J Pharm Biopharm. 2014 Sep;88(1):48-55. doi: 10.1016/j.ejpb.2014.05.002. Epub 2014 May 20.
Ultradeformable vesicles are highly promising tools to enhance the percutaneous transport of different drugs such as tretinoin across the skin barrier and also to increase the formulation stability at absorption site and reduce the drug induced irritation.
Topical delivery of tretinoin-loaded ultradeformable vesicles (tretinoin-UDV) was evaluated concerning different studies, such as: the release and permeation profiles (tape stripping); skin penetration (fluorescence analysis); induced electrical changes in skin barrier properties; cytotoxicity (Trypan Blue assay) and skin irritation in in vivo conditions (Draize test). The novel formulation performance was also compared to a commercial tretinoin formulation regarding in vivo studies.
It was obtained a sustained and controlled drug release, as expected for UDV formulation. In addition, a dermal delivery was observed regarding the permeation study since it was not detected any drug amount in the receptor phase after 24h. Nile Red-UDV stained intensively mostly in the stratum corneum, corroborating the tape stripping results. Tretinoin-UDV decreased skin resistance, suggesting its ability to induce skin barrier disruption. Finally, the formulation vehicle (empty UDV) and tretinoin-UDV were not toxic under in vitro and in vivo conditions, at least, at 5×10(-3)mg/mL and 0.5mg/mL of tretinoin, respectively.
Tretinoin-UDV is a promising delivery system for tretinoin dermal delivery without promoting skin irritation (unlike other commercial formulations), which is quite advantageous for therapeutic purpose.
超可变形囊泡是极具前景的工具，可增强不同药物（如维甲酸）经皮穿过皮肤屏障的运输能力，还能提高制剂在吸收部位的稳定性并减少药物引起的刺激。
针对不同研究评估了载维甲酸超可变形囊泡（维甲酸 - UDV）的局部给药情况，这些研究包括：释放和渗透曲线（胶带剥离法）；皮肤渗透（荧光分析）；皮肤屏障特性的诱导电变化；细胞毒性（台盼蓝试验）以及体内条件下的皮肤刺激性（Draize试验）。还将这种新型制剂的性能与一种市售维甲酸制剂进行了体内研究比较。
正如UDV制剂所预期的那样，实现了药物的持续和可控释放。此外，在渗透研究中观察到了真皮给药，因为在24小时后受体相中未检测到任何药物量。尼罗红 - UDV主要在角质层中强烈染色，这与胶带剥离结果相符。维甲酸 - UDV降低了皮肤电阻，表明其具有破坏皮肤屏障的能力。最后，制剂载体（空UDV）和维甲酸 - UDV在体外和体内条件下均无毒，至少分别在维甲酸浓度为5×10(-3)mg/mL和0.5mg/mL时无毒。
维甲酸 - UDV是一种有前景的维甲酸真皮给药系统，不会引起皮肤刺激（与其他市售制剂不同），这对于治疗目的非常有利。
