Cancer Prevention Research 2019 Apr;12(4):225-236. | https://doi.org/10.1158/1940-6207.CAPR-18-0437
Vinod Vijayakurup, Arun Kumar T Thulasidasan, Mohan Shankar G, Archana.P Retnakumari, C Devika Nandan, Jannet Somaraj, Jayesh Antony, Vijai V Alex, Balachandran S Vinod, Vijayasteltar Belsamma Liju, Sankar Sundaram, G S Vinod Kumar and Ruby John Anto
Abstract
The rate of lung cancer incidence is alarmingly mounting, despite the
decline of smoking and tobacco consumption. Recent reports indicate a
very high correlation between the growing fast food culture and lung
cancer incidence. Benzo[a]pyrene (B[a]P) is a potent carcinogen
abundantly present in grilled and deep-fried food and in tobacco smoke.
Our previous studies have proved the efficacy of curcumin in curbing
B[a]P-induced lung carcinogenesis. However, the poor pharmacokinetic
profile of the compound considerably hampers its potential as an
effective chemopreventive. This study was intended to evaluate whether
encapsulation of curcumin in chitosan nanoparticles can improve the
cellular uptake and prolong the tissue retention of curcumin yielding
better chemoprevention. The curcumin-loaded chitosan nanoparticles
(chitosan nanocurcumin) exhibited a size of 170-200 nm in transmission
electron microscopy. In vitro drug release studies
showed sustained release of curcumin over a period of approximately 180
hours and excellent intracellular uptake and cytotoxicity in lung cancer
cells. Bioavailability studies using healthy Swiss albino mice
demonstrated drastic enhancement in lung localization of chitosan
nanocurcumin compared with free curcumin. Toxicologic evaluation using
chronic toxicity model in Swiss albino mice confirmed the pharmacologic
safety of the formulation. Moreover, the formulation, even at a dose
equivalent to one fourth that of free curcumin, exhibits better efficacy
in reducing tumor incidence and multiplicity than free curcumin, thereby
hampering development of B[a]P-induced lung adenocarcinomas in Swiss
albino mice. Hence, our study underscores the supremacy of the
formulation over free curcumin and establishes it as a potential
chemopreventive and oral supplement against environmental
carcinogenesis.