Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, India.
Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, India.
Eur J Pharm Biopharm. 2023 May;186:18-29. doi: 10.1016/j.ejpb.2023.03.004. Epub 2023 Mar 15.
Temozolomide (TMZ) is one of the best choices for treating glioblastoma. However, due to the short plasma half-life, only 20-30 % brain bioavailability can be achieved using traditional formulations. In the present study, PEGylated liposomes and lyotropic liquid crystals (LLCs) were developed and investigated to prolong the plasma circulation time of TMZ. Industrially feasible membrane extrusion and modified hot melt emulsification techniques were utilized during the formulation. Liposomes and LLCs in the particle size range of 80-120 nm were obtained with up to 50 % entrapment efficiency. The nanocarriers were found to show a prolonged release of up to 72 h. The cytotoxicity studies in glioblastoma cell lines revealed a ∼1.6-fold increased cytotoxicity compared to free TMZ. PEGylated liposomes and PEGylated LLCs were found to show a 3.47 and 3.18-fold less cell uptake in macrophage cell lines than uncoated liposomes and LLCs, respectively. A 1.25 and 2-fold increase in the plasma t was observed with PEGylated liposomes and PEGylated LLCs, respectively, compared to the TMZ when administered intravenously. Extending plasma circulation time of TMZ led to significant increase in brain bioavailability. Overall, the observed improved pharmacokinetics and biodistribution of TMZ revealed the potential of these PEGylated nanocarriers in the efficient treatment of glioblastoma.
替莫唑胺（TMZ）是治疗胶质母细胞瘤的最佳选择之一。然而，由于其血浆半衰期较短，传统制剂的脑生物利用度仅为 20-30%。在本研究中，开发并研究了聚乙二醇化脂质体和溶致液晶（LLC）来延长 TMZ 的血浆循环时间。在配方中使用了工业可行的膜挤出和改良的热熔乳化技术。获得了粒径在 80-120nm 范围内的脂质体和 LLC，包封效率高达 50%。纳米载体的释放时间延长至 72 小时。在胶质母细胞瘤细胞系中的细胞毒性研究表明，与游离 TMZ 相比，细胞毒性增加了约 1.6 倍。与未涂层的脂质体和 LLC 相比，PEG 化脂质体和 PEG 化 LLC 分别在巨噬细胞系中的细胞摄取量减少了 3.47 倍和 3.18 倍。与 TMZ 静脉给药相比，PEG 化脂质体和 PEG 化 LLC 的血浆 t 分别延长了 1.25 倍和 2 倍。延长 TMZ 的血浆循环时间导致脑生物利用度显著增加。总的来说，TMZ 的药代动力学和生物分布得到了改善，这表明这些 PEG 化纳米载体在胶质母细胞瘤的有效治疗中有潜力。
