Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth, Pune, India.
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Int J Pharm. 2023 Apr 25;637:122894. doi: 10.1016/j.ijpharm.2023.122894. Epub 2023 Mar 28.
The therapeutics available for cancer treatment have the major hurdle of site-specific delivery of anti-cancer drugs to the tumor site and non-target specific side effects. The standard therapy for ovarian cancer still poses numerous pitfalls due to the irrational use of drugs affecting healthy cells. As an appealing approach, nanomedicine could revamp the therapeutic profile of anti-cancer agents. Owing to the low manufacturing cost, increased biocompatibility, and modifiable surface properties, lipid-based nanocarriers, particularly solid lipid nanoparticles (SLN), have remarkable drug delivery properties in cancer treatment. Given the extra-ordinary benefits, we developed anti-neoplastic (paclitaxel) drug-loaded SLN (PTX-SLN) and functionalized with N-acetyl-d-glucosamine (GLcNAc) (GLcNAc-PTX-SLN) to reduce the rate of proliferation, growth, and metastasis of ovarian cancer cells over-expressing GLUT1 transporters. The particles presented considerable size and distribution while demonstrating haemocompatibility. Using GLcNAc modified form of SLNs, confocal microscopy, MTT assay, and flow cytometry study demonstrated higher cellular uptake and significant cytotoxic effect. Also, molecular docking results established excellent binding affinity between GLcNAc and GLUT1, complimenting the feasibility of the therapeutic approach in targeted cancer therapy. Following the compendium of target-specific drug delivery by SLN, our results demonstrated a significant response for ovarian cancer therapy.
治疗癌症的方法主要面临的难题是将抗癌药物靶向递送到肿瘤部位和非靶向的副作用。由于药物对健康细胞的不合理使用，卵巢癌的标准治疗仍然存在许多问题。作为一种有吸引力的方法，纳米医学可以改变抗癌药物的治疗特性。由于制造成本低、生物相容性高和表面性质可修饰，基于脂质的纳米载体，特别是固体脂质纳米粒（SLN），在癌症治疗中有显著的药物传递特性。鉴于其卓越的优势，我们开发了载有抗肿瘤药物（紫杉醇）的 SLN（PTX-SLN），并用 N-乙酰-d-葡萄糖胺（GLcNAc）对其进行功能化（GLcNAc-PTX-SLN），以降低过度表达 GLUT1 转运蛋白的卵巢癌细胞的增殖、生长和转移速度。这些颗粒表现出相当大的尺寸和分布，同时具有血液相容性。使用 GLcNAc 修饰的 SLN，共聚焦显微镜、MTT 测定和流式细胞术研究表明，细胞摄取率更高，细胞毒性作用显著。此外，分子对接结果表明 GLcNAc 与 GLUT1 之间具有极好的结合亲和力，这证实了该治疗方法在靶向癌症治疗中的可行性。根据 SLN 的靶向药物传递综述，我们的结果表明，该方法对卵巢癌治疗有显著的反应。
