Title: Augmentation of anti-tumour activity of cisplatin by pectin nano-conjugates in B-16 mouse model: pharmacokinetics and in-vivo biodistribution of radio-labelled, hydrophilic nano-conjugates

Authors: Anita Kamra Verma; Abhishek Chanchal; Krishna Chutani

Addresses: Nano-Bio-tech Laboratory, Department of Zoology, K.M. College, University of Delhi, Delhi 110007, India ' Nano-Bio-tech Laboratory, Department of Zoology, K.M. College, University of Delhi, Delhi 110007, India ' Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Br. Majumdar Road, Timar Pur, New Delhi-07, India

Abstract: Nanoconjugates have matured from simple devices to multifunctional, biodegradable, non-toxic and non-immunogenic constructs, capable of delivering synergistically functioning drugs in vivo. The present study evaluates the efficacy of drug polymer self folding nano-conjugates of pectin-cisplatin to enhance blood circulating levels of cisplatin. Physical characterisation was done by DLS, zeta potential and TEM. Pharmacokinetics and bio-distribution of the ^99mTc labelled pectin-cisplatin nano-conjugates and cisplatin per se was performed at various time points in normal and tumour bearing C57Bl6 mice, and Gamma Scintigraphic imaging done in rabbits. Nano-conjugates showed prolonged plasma residence and increased t_1/2 of cisplatin ∼11.26 h. Altered bio-distribution was observed with nano-conjugates, as negligible accumulation of cisplatin was observed in kidney and has the potential to reduce nephrotoxicity. We preliminarily investigated the chemotherapeutic potential of pectin-cisplatin nanoconjugates, cisplatin and pectin on murine melanoma B16 cells in vitro and in-vivo. Mouse B16F10 melanoma cells were cultured in vitro in DMEM media containing 10% FBS, nonessential amino acids and antibiotics in a 5% CO₂ incubator at 37°C and the effect of pectin, cisplatin singly and in combination i.e., pectin-cisplatin conjugate was assessed by MTT assay. In vivo studies were performed by solid tumour models viz., B16F10 on C57Bl6 mice. Antitumour efficacy was monitored by measuring tumour burden. Combination therapy led to significantly delayed tumour growth and improved survival in vivo. Tumour regression studies clearly indicate that pectin augments the activity of cisplatin as a three-fold reduction in tumour volume was observed.

Keywords: pectin; cisplatin; hydrophilic nanoconjugates; zeta potential; biodistribution; ^99mTc-labelled; tumour regression; nephrotoxicity; DDS; CDDP; pharmacokinetics; drug delivery; cancer drugs; murine melanoma; blood circulation levels; kidney accumulation; nanotechnology.

DOI: 10.1504/IJNT.2012.049452

International Journal of Nanotechnology, 2012 Vol.9 No.10/11/12, pp.872 - 886

Published online: 04 Oct 2012 *

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