TY - JOUR

T1 - Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

AU - Swarnakar, Nitin K

AU - Thanki, Kaushik

AU - Jain, Sanyog

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/8

Y1 - 2014/8

N2 - 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.

AB - 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.

KW - Administration, Intravenous

KW - Administration, Oral

KW - Animals

KW - Antibiotics, Antineoplastic

KW - Breast Neoplasms

KW - Cardiotoxicity

KW - Cell Line, Tumor

KW - Doxorubicin

KW - Drug Therapy, Combination

KW - Female

KW - Humans

KW - Liquid Crystals

KW - Nanoparticles

KW - Rats, Sprague-Dawley

KW - Ubiquinone

KW - Vitamins

KW - Comparative Study

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.nano.2014.03.003

DO - 10.1016/j.nano.2014.03.003

M3 - Journal article

C2 - 24637217

VL - 10

SP - 1231

EP - 1241

JO - Nanomedicine: Nanotechnology, Biology and Medicine

JF - Nanomedicine: Nanotechnology, Biology and Medicine

SN - 1549-9634

IS - 6

ER -