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

Abstract

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 (1)H 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±10nm, zeta potential: -17.5±0.2mV) 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.

• Authors: Vaibhav Khare, Amarinder Singh, Girish Mahajan, Noor Alam, Smit Kour, Mehak Gupta, Ajay Kumar, Gurdarshan Singh, Shashank K Singh, Ajit K Saxena, Dilip M Mondhe, Prem N Gupta
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 92 Pg. 183-93 (Sep 20 2016) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 27404580 (Publication Type: Journal Article)
• Copyright: Copyright © 2016. Published by Elsevier B.V.

Chemical References

• Antimetabolites, Antineoplastic
• Drug Carriers
• Polyesters
• methoxypolyethyleneglycol-poly(lactic-co-glycolic acid)
• Deoxycytidine
• Polyethylene Glycols
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Carcinoma, Ehrlich Tumor (drug therapy, pathology)
• Cell Line
• Cell Line, Tumor
• Cell Survival (drug effects)
• Deoxycytidine (administration & dosage, analogs & derivatives, chemistry, pharmacokinetics, therapeutic use)
• Drug Carriers (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Drug Liberation
• Erythrocytes (drug effects)
• Female
• Hemolysis (drug effects)
• Humans
• Male
• Mice, Inbred BALB C
• Nanoparticles (administration & dosage, chemistry, therapeutic use)
• Polyesters (chemistry)
• Polyethylene Glycols (chemistry)
• Rats
• Tumor Burden (drug effects)
• Gemcitabine