Long-circulatory nanoparticles for gemcitabine delivery: Development and investigation of pharmacokinetics and in-vivo anticancer efficacy

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• 作者：Vaibhav Khare^a ; Amarinder Singh^b ; Girish Mahajan^c ; Noor Alam^a ; Smit Kour^b ; Mehak Gupta^c ; Ajay Kumar^c ; Gurdarshan Singh^a ; ^b ; ^d ; Shashank K. Singh^c ; ^d ; Ajit K. Saxena^c ; Dilip M. Mondhe^c ; ^d ; ^{dmmondhe@iiim.res.in" class="auth_mail" title="E-mail the corresponding author} ; Prem N. Gupta^a ; ^b ; ^d ; ^{pngupta@iiim.res.in" class="auth_mail" title="E-mail the corresponding author} ; ^{pngupta10@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Gemcitabine hydrochloride (PubChem CID ; 60749) ; Poly(dl-lactic-co-glycolic acid) (PubChem CID ; 23111554) ; Ethylene glycol (PubChem CID ; 174) ; Dicyclohexylcarbodiimide (PubChem CID ; 10868) ; N-hydroxysuccinimide (PubChem CID ; 80170)
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：20 September 2016
• 年：2016
• 卷：92
• 期：Complete
• 页码：183-193
• 全文大小：1249 K

文摘

The anticancer potential of gemcitabine, a nucleoside analog, is compromised due to the enzymatic degradation into inactive form leading to the short half-life in systemic circulation. Novel delivery strategies are required to improve therapeutic efficacy of this potential drug. Monomethoxy polyethylene glycol amine-polylactide-co-glycolide (mPEG-PLGA) co-polymer was synthesized and characterized by FTIR and ¹H NMR. Gemcitabine loaded mPEG-PLGA nanoparticles (NPs) were developed and investigated for pharmacokinetic profile and in vivo anticancer activity. The mPEG-PLGA NPs (size: 267 ± 10 nm, zeta potential: − 17.5 ± 0.2 mV) exhibited sustained drug release profile and were found to be compatible with blood. The mPEG-PLGA NPs were able to evade the uptake by macrophages (i.e. THP-1 and J774A) by reducing the adsorption of proteins on the surface of NPs. The enhanced cellular uptake and cell cytotoxicity was observed by mPEG-PLGA NPs in MiaPaCa-2 and MCF-7 cells. The half-life of gemcitabine in mPEG-PLGA NPs was remarkably enhanced (19 folds) than native gemcitabine. Further, the pharmacokinetic modulation of gemcitabine using mPEG-PLGA-NPs was translated in improved anticancer efficacy as compared to native gemcitabine in Ehrlich ascites bearing Balb-c mice. The results demonstrated the potential of long-circulatory nanoparticles in improving the pharmacokinetic profile and in-turn the anticancer efficacy of gemcitabine.