Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin
UNLABELLED: Present study focuses on enhancing oral antitumor efficacy and safety of Dox-LCNPs in combination with CoQ10-LCNPs. Drug-loaded-LCNPs were prepared by solvent-diffusion-evaporation method and optimized. Median effect analysis suggested dose-reduction-index of 16.84- and 5.047-fold and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor efficacy was found to be significantly higher (~1.76- and ~4.5-fold) for the combination as compared to Dox-LCNPs (per oral) and Adriamycin (i.v.) respectively. Notably, level of residual tumor burden was insignificant (P>0.05) after 30days in case of combination and LipoDox® (i.v.). Interestingly, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme Q10 and doxorubicin. The nano-conjugates not only provided an enhanced oral treatment option for a tumor model, but prevented cardiotoxicity, a major complication of this drug when delivered via conventional methods.
Nanomedicine: Nanotechnology, Biology and Medicine, 2014, Vol 10, Issue 6, p. 1231-41