School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China.
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People's Republic of China.
Int J Pharm. 2023 Aug 25;643:123256. doi: 10.1016/j.ijpharm.2023.123256. Epub 2023 Jul 22.
The transdermal drug delivery system (TDDS) is an effective strategy for the treatment of melanoma with fewer side effects and good biocompatible, but the skin penetration of drugs should be further promoted. Here, we proposed a new system that combined curcumin liposomes (Cur-Lips) with skin-penetrating peptides to promote skin penetration ability. However, the preparation of Cur-Lips has drawbacks of instability and low entrapment efficiency by the traditional methods. We thus innovatively designed and applied a microfluidic chip to optimize the preparation of Cur-Lips. Cur-Lips exhibited a particle size of 106.22 ± 4.94 nm with a low polydispersity index (＜0.3) and high entrapment efficiency of 99.33 ± 1.05 %, which were prepared by the microfluidic chip. The Cur-Lips increased the skin penetration capability of Cur by 2.76 times compared to its solution in vitro skin penetration experiment. With the help of skin-penetrating peptide TD-1, the combined system further promoted the skin penetration capability by 4.48 times. The (TD-1 + Cur-Lips) system also exhibited a superior inhibition effect of the tumor to B16F10 in vitro. Furthermore, the topical application of (TD-1 + Cur-Lips) gel suppressed melanoma growth in vivo, and induced tumor cell apoptosis in tumor tissues. The skin-penetration promotion mechanism of the system was investigated. It was proved that the system could interact with the lipids and keratin on the stratum corneum to promote the Cur distribute into the stratum corneum through hair follicles and sweat glands. We proved that the microfluidic chips had unique advantages for the preparation of liposomes. The innovative combined system of liposomes and biological transdermal enhancers can effectively promote the skin penetration effect of drugs and have great potential for the prevention and treatment of melanoma.
透皮给药系统（TDDS）是一种治疗黑色素瘤的有效策略，具有较少的副作用和良好的生物相容性，但药物的皮肤渗透仍需进一步促进。在这里，我们提出了一种新的系统，将姜黄素脂质体（Cur-Lips）与透皮肽结合，以促进皮肤穿透能力。然而，传统方法制备的 Cur-Lips 存在不稳定性和低包封率的缺点。因此，我们创新性地设计并应用微流控芯片来优化 Cur-Lips 的制备。通过微流控芯片制备的 Cur-Lips 粒径为 106.22±4.94nm，多分散指数（＜0.3）低，包封率为 99.33±1.05%。与体外皮肤渗透实验相比，Cur-Lips 增加了 Cur 的皮肤渗透能力 2.76 倍。在透皮肽 TD-1 的帮助下，联合系统进一步促进了 4.48 倍的皮肤渗透能力。（TD-1+Cur-Lips）系统在体外对 B16F10 也表现出更好的抑制作用。此外，（TD-1+Cur-Lips）凝胶的局部应用抑制了体内黑色素瘤的生长，并诱导肿瘤组织中肿瘤细胞凋亡。研究了该系统的皮肤渗透促进机制。证明该系统可以与角质层中的脂质和角蛋白相互作用，通过毛囊和汗腺促进 Cur 分布到角质层中。证明微流控芯片在制备脂质体方面具有独特的优势。脂质体和生物透皮增强剂的创新联合系统可以有效地促进药物的皮肤渗透效果，在黑色素瘤的预防和治疗方面具有巨大的潜力。
