Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.
ACS Nano. 2020 Jun 23;14(6):7227-7236. doi: 10.1021/acsnano.0c02343. Epub 2020 May 18.
Conventional melanoma therapies suffer from the toxicity and side effects of repeated treatments due to the aggressive and recurrent nature of melanoma cells. Less-invasive topical chemotherapies by utilizing polymeric microneedles have emerged as an alternative, but the sustained, long-lasting release of drug cargos remains challenging. In addition, the size of the microneedles is relatively bulky for the small, curvilinear, and exceptionally sensitive cornea for the treatment of ocular melanoma. Here, we report a design of bioresorbable, miniaturized porous-silicon (p-Si) needles with covalently linked drug cargos at doses comparable to those of conventional polymeric microneedles. The p-Si needles are built on a water-soluble film as a temporary flexible holder that can be intimately interfaced with the irregular surface of living tissues, followed by complete dissolution with saline solution within 1 min. Consequently, the p-Si needles remain embedded inside tissues and then undergo gradual degradation, allowing for sustained release of the drug cargos. Its utility in unobtrusive topical delivery of chemotherapy with minimal side effects is demonstrated in a murine melanoma model.
传统的黑色素瘤疗法由于黑色素瘤细胞具有侵袭性和复发性,因此会因反复治疗而产生毒性和副作用。利用聚合物微针的微创局部化疗已成为一种替代方法,但药物有效负载的持续、长效释放仍然具有挑战性。此外,对于治疗眼部黑色素瘤来说,微针的尺寸相对较大,因为角膜小而弯曲,而且异常敏感。在这里,我们报告了一种生物可吸收的、小型化的多孔硅(p-Si)针的设计,这些针具有共价连接的药物有效负载,其剂量与传统聚合物微针相当。p-Si 针构建在水溶性薄膜上,作为临时柔性支架,可以与活体组织的不规则表面紧密结合,然后在 1 分钟内用生理盐水完全溶解。因此,p-Si 针仍然嵌入在组织内部,然后逐渐降解,允许药物有效负载持续释放。在小鼠黑色素瘤模型中,证明了其在无干扰的局部递送化疗药物方面具有最小的副作用的用途。