Improved oral efficacy of epirubicin through polymeric nanoparticles: pharmacodynamic and toxicological investigations

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.

Keywords:

• Biodistribution
• Ehrlich’s ascites
• Epirubicin
• oral administration
• tumor inhibition

Acknowledgements

The authors acknowledge the contribution of Fresenius Kabi and Evonik Degussa Pvt. Ltd. for providing gift samples. The authors are indebted to Jamia Millia Islamia, and SAIF (AIIMS), New Delhi India to carry out SEM and TEM analysis. Assistance rendered by Dr. A K Tiwari and Mr. Mohammad Ibrahim in animal studies is also duly acknowledged.

Declaration of interest

There is no academic, financial, personal and commercial conflict of interest of authors. Authors are thankful to Jamia Hamdard, for facilitating research activities and Department of Biotechnology (DBT) for financial support.