Design of temozolomide-loaded proliposomes and lipid crystal nanoparticles with industrial feasible approaches: comparative assessment of drug loading, entrapment efficiency, and stability at plasma pH

Abstract

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.