Abstract

In recent years, the incidence of skin cancer has increased worldwide, presenting a significant burden on healthcare services. Chemotherapy intervention is often not appropriate for all patients due to localized adverse effects on skin physiology. The aim of this study was, therefore, to consider the development of a novel phytochemical-based deformable liposomal formulation suspended in an aqueous gel for the controlled-release of naringenin. Naringenin is an antioxidant, free radical scavenger, anti-inflammatory agent, and immune system modulator thus may be potentially useful as a pharmacological anti-cancer agent. Formulated liposomes incorporating an increasing loading of Tween 20 (from 0% w/w to 10% w/w) demonstrated a significant decrease in deformability index (DI) (80.71 ± 2.02–59.17 ± 4.42 %), indicating an increase in elasticity. The release of naringenin over 24 h was directly affected by Tween-20 concentration, decreasing from 100.72%±4.98% to 79.53%±3.68% for 0% and 2% w/w Tween 20, respectively. Further, the incorporation of deformable liposomes into hydroxyethylcellulose (HEC) and hydroxypropyl methylcellulose (HPMC) gels resulting in a further retardation of naringenin release, 23.21%±1.17% and 19.83%±1.50%, respectively, over 24 h. Incubation of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate-loaded liposomes with human dermal fibroblast (HDF) and keratinocyte cells demonstrated intracellular accumulation within 2 h, confirming deformable liposomes may be beneficial in improving drug penetration across dermal cells and would be valuable in emerging controlled-release formulations.

摘要

近年来，世界范围内皮肤癌的发病率呈上升趋势，给医疗保健服务带来了沉重的负担。由于对皮肤生理的局部不利影响，化疗干预通常不适用于所有患者。因此，本研究的目的是考虑开发一种新型的基于植物化学的可变形脂质体制剂，该制剂悬浮在水凝胶中以控制柚皮素的释放。柚皮素是一种抗氧化剂、自由基清除剂、抗炎剂和免疫系统调节剂，因此可能潜在地用作药理学抗癌剂。含有增加的吐温 20 负载（从 0% w/w 到 10% w/w）的配方脂质体表现出变形指数 (DI) 显着降低（80.71 ± 2.02–59.17 ± 4.42%），表明弹性增加。柚皮素在 24 小时内的释放直接受 Tween-20 浓度的影响，0% 和 2% w/w Tween 20 分别从 100.72%±4.98% 下降到 79.53%±3.68%。此外，将可变形脂质体掺入羟乙基纤维素 (HEC) 和羟丙基甲基纤维素 (HPMC) 凝胶中，导致柚皮素释放的进一步延迟，分别为 23.21%±1.17% 和 19.83%±1.50%，超过 24 小时。负载 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate 的脂质体与人真皮成纤维细胞 (HDF) 和角质形成细胞一起孵育在 2 小时内显示出细胞内积聚，证实可变形脂质体可能有助于改善药物穿透真皮细胞，在新兴的控释制剂中很有价值。