School of Pharmaceutical Sciences , Nanjing Tech University , Nanjing 211816 , China.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials , China Pharmaceutical University , Nanjing 210009 , China.
ACS Nano. 2018 Oct 23;12(10):9693-9701. doi: 10.1021/acsnano.8b03800. Epub 2018 Sep 5.
Topical administration of anticancer drugs provides a potential chemotherapeutic modality with high patient compliance for cutaneous melanoma. However, the drug delivery efficiency is highly limited by physiological barriers from the skin to the tumor, which cannot acquire desired therapeutic efficacy. Herein, we propose a paintable oligopeptide hydrogel containing paclitaxel (PTX)-encapsulated cell-penetrating-peptide (CPP)-modified transfersomes (PTX-CTs) to enhance transdermal PTX delivery for topical melanoma treatment. After being plastered on the skin above the melanoma tumor, the PTX-CTs-embedded hydrogel (PTX-CTs/Gel) as a patch provided prolonged retention capacity of the PTX-CTs on the skin. The PTX-CTs with superior deformability could efficiently squeeze through the channels in the stratum coreum, and the surfactant components improved the fluidity of the lipid molecules in the stratum corneum to further enhance the skin permeation. Moreover, the CPP modification rendered the PTX-CT-enhanced penetration in the skin and tumor stroma as well as efficient transportation in the tumor cells. The PTX-CTs were shown to effectively slow the tumor growth in combination with the systemic chemotherapy using Taxol, the commercial PTX formulation on the xenograft B10F16 melanoma mouse model.
局部给予抗癌药物为皮肤黑色素瘤提供了一种潜在的化疗方式，患者顺应性高。然而，药物输送效率受到皮肤到肿瘤的生理屏障的高度限制，无法获得所需的治疗效果。在此，我们提出了一种可涂敷的含有紫杉醇（PTX）包封的穿膜肽（CPP）修饰的传递体（PTX-CTs）的短肽水凝胶，以增强透皮 PTX 递送，用于局部治疗黑色素瘤。PTX-CTs 包封的水凝胶（PTX-CTs/Gel）贴剂贴在黑色素瘤肿瘤上方的皮肤上后，可延长 PTX-CTs 在皮肤上的保留能力。具有优异变形能力的 PTX-CTs 可有效地挤过角质层的通道，表面活性剂成分改善了角质层中脂质分子的流动性，进一步增强了皮肤渗透。此外，CPP 修饰使 PTX-CT 在皮肤和肿瘤基质中的穿透增强，并在肿瘤细胞中实现有效的运输。PTX-CTs 与 Taxol（一种商业化的 PTX 制剂）联合全身化疗，可有效抑制异种移植 B10F16 黑色素瘤小鼠模型中的肿瘤生长。
