Waghule Tejashree, Rapalli Vamshi Krishna, Singhvi Gautam, Gorantla Srividya, Khosa Archana, Dubey Sunil Kumar, Saha Ranendra Narayan
Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, India.
IDRS Labs Pvt. Ltd, Bommasandra Industrial area, Bangalore, India.
J Liposome Res. 2021 Jun;31(2):158-168. doi: 10.1080/08982104.2020.1748648. Epub 2020 Apr 17.
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 this 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.
替莫唑胺是一种被批准用于治疗胶质母细胞瘤的药物，其口服生物利用度为100%，但在生理pH值下会降解，因此半衰期很短，脑生物利用度仅为20%-30%。由于其两亲性，已报道的纳米制剂药物载量较低。这项工作的目的是制备基于脂质的药物递送系统，通过延长药物释放和循环时间来提高脑生物利用度，以克服现有疗法的局限性并可能减少副作用。所获得的纳米载体尺寸小于300nm，所获得的多分散指数（PDI）小于0.3。与其他已报道的替莫唑胺纳米载体相比，所设计的制剂显示出更高的包封率。与纯药物6小时的释放时间相比，所设计的制剂显示出药物释放时间从12小时延长至20小时。在12小时结束时，约95%的纯药物在血浆pH值下被降解，而当包裹在脂质晶体纳米颗粒和前体脂质体中时，分别只有68%和77%被降解。此外，药代动力学和动物研究可以证实这些制剂在提高脑生物利用度方面的潜力。
