Jain, A.K.Swarnakar, N.K.Das, M.Godugu, C.Singh, R.P.Rao, P.R.Jain, S.2018-07-142024-08-132018-07-142024-08-132011Jain, A. K., Swarnakar, N. K., Das, M., Godugu, C., Singh, R. P., Rao, P. R., & Jain, S. (2011). Augmented anticancer efficacy of doxorubicin-loaded polymeric nanoparticles after oral administration in a breast cancer induced animal model. Molecular Pharmaceutics, 8(4), 1140-1151. doi: 10.1021/mp200011f1543838410.1021/mp200011fhttp://10.2.3.109/handle/32116/1246The present investigation reports an extensive evaluation of in vitro and in vivo anticancer efficacy of orally administered doxorubicin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Dox-NPs) in a breast cancer induced animal model. Spherically shaped Dox-NPs were prepared with an entrapment efficiency and particle size of 55.40 ? 2.30% and 160.20 ? 0.99 nm, respectively, and freeze-dried with 5% trehalose using stepwise freeze-drying. Cytotoxicity, as investigated on C127I cell line, revealed insignificant differences between the IC 50 of free Dox and Dox-NPs treated cells in the first 24 h, while higher cytotoxicity was demonstrated by Dox-NPs, following 72 h of incubation. Confocal laser scanning microscopy (CLSM) imaging corroborated that nanoparticles were efficiently localized into the nuclear region of C127I cells. The cellular uptake profile of Dox-NPs revealed both time and concentration dependent increases in the Caco-2 cell uptake as compared to the free Dox solution. Further, Dox-NPs significantly suppressed the growth of breast tumor in female Sprague-Dawley (SD) rats upon oral administration. Finally, orally administered Dox-NPs showed a marked reduction in cardiotoxicity when compared with intravenously injected free Dox as also evident by the increased level of malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine phosphokinase (CK-MB) and reduced levels of glutathione (GSH) and superoxide dismutase (SOD). The reduced cardiotoxicity of orally administered Dox-NPs was also confirmed by the major histopathological changes in the heart tissue after the treatments of intravenously injected free Dox and orally delivered Dox-NPs. ? 2011 American Chemical Society.en-USDoxorubicinPLGA nanoparticlesNuclear localizationOral deliveryArticlehttps://pubs.acs.org/doi/abs/10.1021/mp200011f