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

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• 作者：Jitender Madan ; PhD^a ; Ravi Shankar Pandey ; PhD^b ; Vikas Jain ; PhD^c ; Om Prakash Katare ; PhD^d ; Ramesh Chandra ; PhD^e ; Anju Katyal ; PhD^e ; ^{anju_katyal@yahoo.com}
• 关键词：Noscapine ; PEGylation ; Lipid nanoparticles ; Cytotoxicity ; Cell cycle ; Pharmacokinetics
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：9
• 期：4
• 页码：492-503
• 全文大小：865 K

文摘

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 ¡À 9.3-nm and 80.5 ¡À 8.9-nm containing 80.4 ¡À 3.2 % and 83.6 ¡À 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; 40.5 ¦ÌM > Nos-SLN; 27.2 ¦ÌM > 20.8 ¦ÌM) 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 400.7 ¦Ìg/g and 313.1 ¦Ìg/g of Nos in comparison to 233.2 ¦Ìg/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 Editor

This 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.