Marathe Sushrut, Shadambikar Gauri, Mehraj Tabish, Sulochana Suresh P, Dudhipala Narendar, Majumdar Soumyajit
Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, MS 38677, USA.
Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, MS 38677, USA.
Pharmaceutics. 2022 May 11;14(5):1034. doi: 10.3390/pharmaceutics14051034.
The management of retinoblastoma (RB) involves the use of invasive treatment regimens. Paclitaxel (PTX), an effective antineoplastic compound used in the treatment of a wide range of malignant tumors, poses treatment challenges due to systemic toxicity, rapid elimination, and development of resistance. The goal of this work was to develop PTX-loaded, α-tocopherol succinate (αTS)-based, nanostructured lipid carrier (NLCs; αTS-PTX-NLC) and PEGylated αTS-PTX-NLC (αTS-PTX-PEG-NLC) to improve ocular bioavailability. The hot homogenization method was used to prepare the NLCs, and repeated measures ANOVA analysis was used for formulation optimization. αTS-PTX-NLC and αTS-PTX-PEG-NLC had a mean particle size, polydispersity index and zeta potential of 186.2 ± 3.9 nm, 0.17 ± 0.03, −33.2 ± 1.3 mV and 96.2 ± 3.9 nm, 0.27 ± 0.03, −39.15 ± 3.2 mV, respectively. The assay and entrapment efficiency of both formulations was >95.0%. The NLC exhibited a spherical shape, as seen from TEM images. Sterilized (autoclaved) formulations were stable for up to 60 days (last time point checked) under refrigerated conditions. PTX-NLC formulations exhibited an initial burst release and 40% drug release, overall, in 48 h. The formulations exhibited desirable physicochemical properties and could lead to an effective therapeutic option in the management of RB.
视网膜母细胞瘤（RB）的治疗涉及采用侵入性治疗方案。紫杉醇（PTX）是一种有效的抗肿瘤化合物，用于治疗多种恶性肿瘤，但由于全身毒性、快速消除和耐药性的产生，给治疗带来了挑战。这项工作的目标是开发基于α-生育酚琥珀酸酯（αTS）的载紫杉醇纳米结构脂质载体（NLCs；αTS-PTX-NLC）和聚乙二醇化αTS-PTX-NLC（αTS-PTX-PEG-NLC），以提高眼部生物利用度。采用热均质法制备NLCs，并使用重复测量方差分析进行配方优化。αTS-PTX-NLC和αTS-PTX-PEG-NLC的平均粒径、多分散指数和zeta电位分别为186.2±3.9 nm、0.17±0.03、-33.2±1.3 mV和96.2±3.9 nm、0.27±0.03、-39.15±3.2 mV。两种制剂的含量测定和包封率均>95.0%。从透射电镜图像可以看出，NLC呈球形。灭菌（高压灭菌）制剂在冷藏条件下最多可稳定60天（检查的最后时间点）。PTX-NLC制剂表现出初始突释，总体上在48小时内药物释放率为40%。这些制剂表现出理想的物理化学性质，可能为RB的治疗提供一种有效的治疗选择。
