Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Medchal, Hyderabad, Telangana, 500078, India.
Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Medchal, Hyderabad, Telangana, 500078, India.
Colloids Surf B Biointerfaces. 2021 Aug;204:111833. doi: 10.1016/j.colsurfb.2021.111833. Epub 2021 May 11.
In the present study, polymeric micelles constituted of N-(2-hydroxypropyl)methacrylamide (HPMA) and methoxypoly(ethylene glycol) (mPEG)-based copolymer, mPEG-b-HPMA was studied for the delivery of an anticancer drug, doxorubicin (DOX) by physically loading the drug into its core. A series of mPEG-b-HPMA copolymers of different molecular weights (MWs, ∼4000-25,000 Da) by using various initiator: monomer feed ratios (1:25/75/125/175) were synthesized by radical polymerization technique. The DOX-loaded micelles were prepared at different drug to polymer ratios by thin film hydration method. Block copolymers were structurally characterized by gel permeation chromatography (GPC), H-NMR spectroscopy, fourier transform infrared spectroscopy (FTIR), and critical micelles concentration studies. The DLS and SEM studies indicated that the micelles were spherical with diameters ∼20-100 nm. The DOX-loaded mPEG-b-HPMA micelles, P6-M1, prepared by the polymer synthesized using initiator: monomer feed ratios of 1:175 and at polymer to drug ratios of 10:1 exhibited low particle sizes (∼46.8 nm), highest drug loading and encapsulation efficiencies (5.6 %, and 63.3 %, respectively) compared to the other tested formulations. Confocal microscopy study indicated that the P6-M1 was taken up by breast cancer cell lines, 4T1, MCF-7, and MDA-MB-231in a time-dependent manner. P6-M1 displayed lower half maximal inhibitory concentration (IC) compared to free drug in all tested treatment durations compared to free DOX. P6-M1 was safe in hemolysis studies with sustained DOX residence in circulation compared to free DOX. The results indicated that mPEG-b-HPMA could be utilized to load DOX effectively, and the optimized nano-micelles, P6-M1 could serve as a promising nanomedicine to treat breast cancer.
在本研究中，研究了由 N-(2-羟丙基)甲基丙烯酰胺 (HPMA) 和甲氧基聚乙二醇 (mPEG) 基共聚物组成的聚合物胶束，通过将药物物理装载到其核心中来递送抗癌药物阿霉素 (DOX)。通过自由基聚合技术，使用不同的引发剂：单体进料比 (1:25/75/125/175) 合成了一系列不同分子量 (MW，约 4000-25000 Da) 的 mPEG-b-HPMA 共聚物。通过薄膜水化法在不同药物与聚合物比下制备载 DOX 的胶束。通过凝胶渗透色谱 (GPC)、H-NMR 光谱、傅里叶变换红外光谱 (FTIR) 和临界胶束浓度研究对嵌段共聚物进行结构表征。DLS 和 SEM 研究表明，胶束呈球形，直径约为 20-100nm。与其他测试配方相比，使用引发剂：单体进料比为 1:175 且聚合物与药物比为 10:1 合成的聚合物制备的载 DOX 的 mPEG-b-HPMA 胶束 P6-M1 具有较小的粒径 (约 46.8nm)、最高的药物载药量和包封效率 (分别为 5.6%和 63.3%)。共聚焦显微镜研究表明，P6-M1 以时间依赖的方式被乳腺癌细胞系 4T1、MCF-7 和 MDA-MB-231 摄取。与游离 DOX 相比，在所有测试治疗时间内，P6-M1 的半最大抑制浓度 (IC) 均低于游离药物。与游离 DOX 相比，P6-M1 在溶血研究中具有较低的 DOX 循环停留时间，安全性更高。结果表明，mPEG-b-HPMA 可有效负载 DOX，优化的纳米胶束 P6-M1 可作为治疗乳腺癌的有前途的纳米药物。
