Arun Kumar, T.Thulasidasan and Archana P., Retnakumari and Mohan , Shankar and Vinod , Vijayakurup and Shabna, Anwar and Sanu , Thankachan and Kavya S. , Pillai and Jisha J., Pillai and Devika, Nandan and Vijai V., Alex and Teena Jacob , Chirayil and Vinod Kumar, G S and Ruby John, Anto (2017) Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy. Oncotarget, 8 (64). 107374-107389. ISSN 1949-2553

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Abstract

Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time. Earlier reports of improvement in bioavailability and retention of drugs upon nanoencapsulation have motivated us in developing various nanoformulations of curcumin, which were found to exhibit significant enhancement in bioavailability and retention time as assessed by our previous in vitro studies. Among the various formulations tested, curcumin-entrapped in PLGA-PEG nanoparticles conjugated to folic acid (PPF-curcumin) displayed maximum cell death. In the present study, we have demonstrated the efficacy of this formulation in augmenting the bioavailability and retention time of curcumin, in vivo, in Swiss albino mice. Further, the acute and chronic toxicity studies proved that the formulation is pharmacologically safe. We have also evaluated its potential in chemosensitizing cervical cancer cells to paclitaxel and have verified the results using cervical cancer xenograft model in NOD-SCID mice. Folic acid conjugation significantly enhanced the efficacy of curcumin in down-regulating various survival signals induced by paclitaxel in cervical cancer cells and have considerably improved its potential in inhibiting the tumor growth of cervical cancer xenografts. The non-toxic nature coupled with improved chemosensitization potential makes PPF-curcumin a promising candidate formulation for clinical trials.

Item Type:	Article
Uncontrolled Keywords:	curcumin, folic acid conjugation, PLGA nanoparticles, bioavailability, chemosensitization
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	20 Apr 2018 05:54
Last Modified:	20 Apr 2018 05:54
URI:	http://rgcb.sciencecentral.in/id/eprint/548

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