a Nanomedicine Lab , Center of Materials Science (CMS), Zewail City of Science and Technology , 6th of October , Giza , Egypt.
b Department of Pharmaceutics and Industrial Pharmacy , College of Pharmacy and Drug Manufacturing, Misr University of Science and Technology (MUST) , 6th of October , Giza , Egypt.
Artif Cells Nanomed Biotechnol. 2018;46(sup3):S641-S650. doi: 10.1080/21691401.2018.1505743. Epub 2018 Oct 8.
Prostate cancer is the most common non-skin cancer among men. Though statins are mainly used as antihyperlipidemic drugs, many studies have reported their proapoptotic and antimetastatic activities on prostate cancer. However, the poor solubility and insufficient delivery of statins in tumor site limit their anticancer activity. The present study introduces an efficient hybrid drug delivery system for the treatment of prostate cancer. The system involves the chemical conjugation of Simvastatin (SMV), a statin compound, to acid-terminated poly(D, L-lactic-co-glycolic acid), PLGA chains followed by its conversion into nanoparticles (NPs), with in situ physical incorporation of more SMV and superparamagnetic iron oxide nanoparticles (SPIONS) into the PLGA NPs. The PLGA-based hybrid nanocarrier system has been designed in such a way to evade the low bioavailability of SMV, confer sustained release of both encapsulated and chemically conjugated SMV, as well as enhancing the anti-cancer effect of the formula via the magnetic targeting with the aid of the encapsulated SPIONS. Magnetism, morphological and physicochemical characterizations, as well as in-vitro release studies were performed. Besides, cytotoxicity on human prostate cancer cell line (PC-3) was evaluated using MTT assay, cell cycle arrest analysis, annexin V/propidium iodide apoptosis assay and ELISA immunoassay for apoptotic enzyme. Optimum PLGA-based hybrid nanocarrier significantly improved the SMV anticancer activity against human prostate cancer cell line through both apoptosis mechanism and retardation of G2-M phase of cell cycle. Also, the up-regulation of the Caspase 3 was aligned with cytotoxicity study's findings.
前列腺癌是男性中最常见的非皮肤癌。尽管他汀类药物主要用作降脂药物，但许多研究已经报道了它们对前列腺癌的促凋亡和抗转移活性。然而，他汀类药物在肿瘤部位的溶解度差和递送不足限制了它们的抗癌活性。本研究介绍了一种用于治疗前列腺癌的高效杂化药物递送系统。该系统涉及将辛伐他汀（SMV）与端酸聚（D，L-丙交酯-共-乙交酯）（PLGA）链进行化学偶联，然后将其转化为纳米颗粒（NPs），同时将更多的 SMV 和超顺磁性氧化铁纳米颗粒（SPIONS）原位物理掺入到 PLGA NPs 中。这种基于 PLGA 的杂化纳米载体系统的设计方式可以避免 SMV 的生物利用度低，使封装和化学偶联的 SMV 持续释放，并通过封装的 SPIONS 的磁性靶向增强配方的抗癌效果。进行了磁性、形态和物理化学特性以及体外释放研究。此外，还通过 MTT 测定、细胞周期阻滞分析、 Annexin V/碘化丙啶凋亡测定和凋亡酶的 ELISA 免疫测定评估了对人前列腺癌细胞系（PC-3）的细胞毒性。基于 PLGA 的最佳杂化纳米载体通过凋亡机制和细胞周期 G2-M 期的延迟显著提高了 SMV 对人前列腺癌细胞系的抗癌活性。此外，Caspase 3 的上调与细胞毒性研究的结果一致。
