Temozolomide is a drug approved for treating glioblastomas which has 100% oral bioavailability but gets degraded at physiological pH thus having very short half-life and only 20-30% brain bioavailability. Due to its amphiphilic nature, reported nanoformulations exhibits poor drug loading. The objective of the present work was to formulate lipid-based drug delivery systems to enhance the brain bioavailability by prolonging the drug release and circulation time of the drug to overcome the limitations of the existing therapies and possible reduction of side effects. The size of the nanocarriers obtained was less than 300 nm and the PDI obtained was less than 0.3. The designed formulation showed higher entrapment efficiency as compared to the other reported nanocarriers of temozolomide. The designed formulations showed prolonged drug release from 12 to 20 h compared to 6 h for the pure drug. About 95% of the pure drug was degraded at plasma pH at the end of 12 h whereas only 68% and 77% was degraded when entrapped inside the lipid crystal nanoparticles and proliposomes respectively. Further, pharmacokinetic and animal studies can confirm the potential of these for improvement of brain bioavailability.

中文翻译：

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用工业可行的方法设计负载替莫唑胺的前脂质体和脂质晶体纳米颗粒：药物负载、包封率和血浆 pH 值稳定性的比较评估

替莫唑胺是一种获批用于治疗胶质母细胞瘤的药物，口服生物利用度为 100%，但在生理 pH 值下会降解，因此半衰期非常短，脑生物利用度仅为 20-30%。由于其两亲性质，报道的纳米制剂表现出较差的载药量。目前工作的目的是制定基于脂质的药物递送系统，通过延长药物的药物释放和循环时间来提高大脑的生物利用度，以克服现有疗法的局限性和可能减少的副作用。获得的纳米载体的尺寸小于300 nm，获得的PDI小于0.3。与其他报道的替莫唑胺纳米载体相比，设计的制剂显示出更高的包埋效率。与纯药物的 6 小时相比，设计的制剂显示药物释放时间延长 12 至 20 小时。在 12 小时结束时，大约 95% 的纯药物在血浆 pH 值下被降解，而当分别被包裹在脂质晶体纳米颗粒和前体脂质体中时，只有 68% 和 77% 被降解。此外，药代动力学和动物研究可以证实这些药物在改善大脑生物利用度方面的潜力。