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 (p50.001), CK-MB (p50.001), AST (p50.001), ALT (p50.001) and MDA levels (p50.001) and reduction in SOD (p50.001) and CAT levels (p50.001) 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.

Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and Therapeutics

“…It has been demonstrated in preclinical studies that the cytotoxic properties of an anticancer drug can be improved after chemical conjugation to HA. HA-targeted nanocarriers, utilizing liposomes or nanoparticles, have been applied for the delivery of several anticancer agents, such as doxorubicin, epirubicin, mitomycin c, and paclitaxel, to CD44 overexpressing cancer cells with improved efficiency. − The diagnostic relevance of HA is also of great importance. Regarding HA in pleural inflammation effusion, assaying HA levels in serum and plasma predicts early diagnoses of complicated parapneumonic pleural effusions that characterize infectious pleuritis .…”

Triple conjugated carbon dots as a nano-drug delivery model for glioblastoma brain tumors

“…Anyhow, to get a significant reduction of cell viability, the required concentrations of C-dots-epi+temo are much higher than the free drugs. This may be due to the lack of a cell targeting ligand, and uderscores the necessity for developing cancer cell targeted drug delivery systems (35)(36)(37) . Using the appropriate targeted system will result in greater cellular uptake and to increase the anticancer activity of the Cdots-drug conjugates.…”

“…Like other anthracyclines, epi intercalates into DNA inducing DNA cleavage assisted by topoisomerase II and inhibits the synthesis of DNA and RNA. In addition to the formation of reactive oxygen species, which increases oxidative damage (14,36) , epirubicin is also approved for the treatment of breast cancer and is being studied as a treatment for solid malignant tumors of stomach, lungs, ovaries and lymphomas.…”

Untitled

“…[6] Several EPI formulated nanosystems have been employed including polymeric micelles, [7] gold nanoparticle (GNP), [3] liposomes, [8] carbon nanotube, [9] and poly-lactide-co-glycolic acid nanoparticles. [10] Nanoemulsion has attracted the attention of researchers in the pharmaceutical and food industries. Nanoemulsion has advantages over conventional drug delivery systems.…”