Improved oral efficacy of epirubicin through polymeric nanoparticles: pharmacodynamic and toxicological investigations. (12th October 2016)

• Record Type: Journal Article
• Authors: Tariq, Mohammad; Alam, Md. Aftab; Singh, Anu T; Panda, Amulya K; Talegaonkar, Sushama
• Is Part Of: Drug delivery. Volume 23:Number 8(2016:Nov.)
• Page Start: 2990
• Page End: 2997
• Publication Date: 2016-10-12
• Subjects: Biodistribution -- Ehrlich's ascites -- Epirubicin -- oral administration -- tumor inhibition; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2015.1136713
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: Epirubicin (EPI) elicits poor-oral bioavailability hence commercially available as injection for intravenous administration which follows a rapid increase and fast decay in plasma drug concentration often needs a frequent dosing that may lead to serious side effects. Aim of the present study is to develop a nanoparticulate system which could deliver epirubicin effectively via oral administration and could eventually promote new concept "chemotherapy at home." In this perspective, epirubicin loaded Poly-lactide-co-glycolic acid nanoparticles (EPI-NPs) were developed by double emulsion evaporation techniques and evaluated for its safety and efficacy against Ehrlich's Ascites (EAT) induced tumor in balb/c mice. In vivo fate of nanoparticles after oral administration in Albino wistar rats was also studied. EPI-NPs showed marked reduction in tumor size ∼40% while tumor size was increased 3.55 and 3.28 folds in control as well as in group treated orally with free epirubicin solution (EPI-S), respectively. Furthermore, toxicological evaluation demonstrated insignificant difference in levels of biomarkers including MDA, CAT, SOD, LDH, CK-MB, AST and ALT when EPI-NPs-oral treatment was compared with control group while levels of these biomarkers were found extremely significant in group treated with EPI-S (i.v). and demonstrated increment in LDH ( p < 0.001), CK-MB ( p < 0.001), AST ( p < 0.001), ALT ( p < 0.001) and MDA levels ( p < 0.001) and reduction in SOD ( p < 0.001) and CAT levels ( p < 0.001) thus confirmed better safety profile of EPI-NPs oral than EPI-S i.v. Biodistribution study demonstrated the presence of NPs in different body organs and blood which suggests probability of NPs translocation across intestine thus at the tumor site.