Hirani Anjali, Grover Aditya, Lee Yong W, Pathak Yashwant, Sutariya Vijaykumar
a Department of Pharmaceutical Sciences , USF College of Pharmacy, University of South Florida , Tampa , FL , USA and.
b School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University , Blacksburg , VA , USA.
Pharm Dev Technol. 2016;21(1):61-7. doi: 10.3109/10837450.2014.965326. Epub 2014 Sep 26.
Age-related macular degeneration (AMD) is one of the leading causes of blindness in the US affecting millions yearly. It is characterized by intraocular neovascularization, inflammation and retinal damage which can be ameliorated through intraocular injections of glucocorticoids. However, the complications that arise from repetitive injections as well as the difficulty posed by targeting the posterior segment of the eye make this interesting territory for the development of novel drug delivery systems (DDS). In the present study, we described the development of a DDS composed of triamcinolone acetonide-encapsulated PEGylated PLGA nanoparticles (NP) incorporated into PLGA-PEG-PLGA thermoreversible gel and its use against VEGF expression characteristic of AMD. We found that the NP with mean size of 208 ± 1.0 nm showed uniform size distribution and exhibited sustained release of the drug. We also demonstrated that the polymer can be injected as a solution and transition to a gel phase based on the biological temperature of the eye. Additionally, the proposed DDS was non-cytotoxic to ARPE-19 cells and significantly reduced VEGF expression by 43.5 ± 3.9% as compared to a 1.53 ± 11.1% reduction with triamcinolone. These results suggest the proposed DDS will contribute to the development of novel therapeutic strategies for AMD.
年龄相关性黄斑变性（AMD）是美国导致失明的主要原因之一，每年影响数百万人。其特征为眼内新生血管形成、炎症和视网膜损伤，可通过眼内注射糖皮质激素得到改善。然而，重复注射引起的并发症以及靶向眼后段所带来的困难，使得这一领域成为新型药物递送系统（DDS）开发的有趣方向。在本研究中，我们描述了一种DDS的开发，该DDS由包裹曲安奈德的聚乙二醇化聚乳酸-羟基乙酸共聚物纳米颗粒（NP）组成，并掺入聚乳酸-羟基乙酸共聚物-聚乙二醇-聚乳酸-羟基乙酸共聚物热可逆凝胶中，用于对抗AMD特征性的血管内皮生长因子（VEGF）表达。我们发现，平均粒径为208±1.0nm的NP呈现出均匀的粒径分布，并表现出药物的持续释放。我们还证明，该聚合物可以作为溶液注射，并根据眼部的生理温度转变为凝胶相。此外，所提出的DDS对ARPE-19细胞无细胞毒性，与曲安奈德使VEGF表达降低1.53±11.1%相比，可使VEGF表达显著降低43.5±3.9%。这些结果表明，所提出的DDS将有助于开发针对AMD的新型治疗策略。
