Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Nanhai Longtime Pharmaceutical Co., Ltd, Foshan 528200, China.
Carbohydr Polym. 2020 Oct 15;246:116650. doi: 10.1016/j.carbpol.2020.116650. Epub 2020 Jun 16.
Microneedles (MNs) technology has many advantages and is an ideal local transdermal drug delivery method. Here we synthesized photocrosslinkable dextran methacrylate (DexMA), and its degree of substitution is 5 % higher than the previous method. We used DexMA hydrogel for the first time to develop a new type of MNs for continuous transdermal administration. The prepared hydrogel MNs can successfully penetrate the epidermal layer and achieve sustained drug release. Doxorubicin (DOX) and trametinib (Tra) are anticancer drugs approved by FDA. Besides, Tra can also reverse P-gp-mediated multidrug resistance (MDR) to effectively block the efflux of DOX by P-gp. We used MNs to simultaneously load Tra and DOX, and achieved synergy in a B16 cell xenograft nude mouse model. The DexMA hydrogel MNs developed in this study can be used to enhance the transdermal delivery of small molecule drugs and reduce systemic toxicity and side effects.
微针（MNs）技术具有许多优势，是一种理想的局部透皮药物传递方法。在这里，我们合成了光交联的葡聚糖甲基丙烯酸酯（DexMA），其取代度比以前的方法高 5%。我们首次使用 DexMA 水凝胶开发了一种新型 MNs，用于持续透皮给药。制备的水凝胶 MNs 可以成功穿透表皮层并实现持续药物释放。多柔比星（DOX）和曲美替尼（Tra）是 FDA 批准的抗癌药物。此外，Tra 还可以逆转 P-糖蛋白介导的多药耐药性（MDR），有效阻止 P-糖蛋白对 DOX 的外排。我们使用 MNs 同时负载 Tra 和 DOX，并在 B16 细胞异种移植裸鼠模型中实现协同作用。本研究开发的 DexMA 水凝胶 MNs 可用于增强小分子药物的透皮递送，降低全身毒性和副作用。
