Poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine improve biological half-life, brain delivery and efficacy in glioblastoma cells

Abstract

Noscapine crosses blood–brain-barrier and inhibits proliferation of glioblastoma cells. However, short plasma half-life and rapid elimination necessitate the administration of multiple injections for successive chemotherapy. Noscapine bearing solid lipid nanoparticles, Nos-SLN and poly (ethylene)-glycol conjugated solid lipid nanoparticles of noscapine, Nos-PEG-SLN of 61.3±9.3-nm and 80.5±8.9-nm containing 80.4±3.2% and 83.6±1.2% of Nos, were constructed. First order kinetic and Higuchi equation were followed to release the Nos at intracellular pH~4.5. Further, a decrease in IC50 (Nos; 40.5μM>Nos-SLN; 27.2μM>20.8μM) and enhanced subG1 population were observed in U87cells. Plasma half-life was enhanced up to ~11-fold and ~5-fold by Nos-PEG-SLN and Nos-SLN which significantly (P<0.05) deposits 400.7μg/g and 313.1μg/g of Nos in comparison to 233.2μg/g by drug solution. This is first report demonstrating a workable approach to regulate the administration of multiple injections of Nos, warranting further in vivo tumor regression study for superior management of brain cancer. From the Clinical EditorThis report describes a possible approach to regulate the administration of multiple injections of Noscapine using solid lipid nanoparticles. The data warrant further in vivo tumor regression studies for optimal management of glioblastoma, a generally very poorly treatable brain cancer.