title: 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.
authors.affiliation: a Department of Pharmaceutics , Faculty of Pharmacy, Jamia Hamdard , New Delhi , India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tariq
authors.affiliation: b Department Pharmacy , Galgotia University , Greater Noida , India.
authors.forename: Md Aftab
authors.initials: MA
authors.lastname: Alam
authors.affiliation: c Dabur Research Foundation , Sahibabad , Ghaziabad , Uttar Pradesh , India , and.
authors.forename: Anu T
authors.initials: AT
authors.lastname: Singh
authors.affiliation: d National Institute of Immunology , New Delhi , India.
authors.forename: Amulya K
authors.initials: AK
authors.lastname: Panda
authors.affiliation: a Department of Pharmaceutics , Faculty of Pharmacy, Jamia Hamdard , New Delhi , India.
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D015251:Epirubicin / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015251:Epirubicin
keywords: Biodistribution; Ehrlich’s ascites; Epirubicin; oral administration; tumor inhibition