Chitosan Encapsulation Enhances the Bioavailability and Tissue Retention of Curcumin and Improves its Efficacy in Preventing B[a]P-induced Lung Carcinogenesis

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]Pinduced 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.

Curcumin Delivery Mediated by Bio-Based Nanoparticles: A Review

“…In a recent study, curcumin loaded chitosan NPs with a size of about 200 nm were prepared to be used as a chemotherapeutic agent for lung cancer. The results of this research confirmed a significant improvement in the cytotoxicity of the drug-loaded nanocarrier and also introduced this type of nanosystem as an oral supplement against environmental carcinogenesis [142]. In another study, curcumin was loaded into a pH-responsive nanocapsule that is composed of mesoporous silica and chitosan for using against the U87MG glioblastoma cancer cell line.…”

Nanotherapeutics in the treatment of acute respiratory distress syndrome

“…These NPs can be delivered directly to the deeper alveolar tissues optimizing lung therapy with efficient drug delivery [ 125 ]. Additionally, the incorporation of curcumin to chitosan NPs has shown an excellent anti-inflammatory effect [ 126 , 127 ].…”

Chitosan Nanoparticles Potentiate the in vitro and in vivo Effects of Curcumin and other Natural Compounds

“…Cur CS NPs evaluation studies were conducted to improve Cur properties for oral administration, since this compound has low bioavailability and aqueous solubility [119]. Vijayakurup et al [120] led in vivo pharmacokinetic studies with Cur CS NPs, which presented greater cellular uptake and Cur retention comparing to the nonencapsulated form, verifying the sustained release of Cur for 180 h. The NPs also demonstrated pharmacological safety, due to their nontoxic properties and, moreover, were able to reduce tumoral incidence and multiplication in pulmonary adenocarcinoma induced by benzo(a)pyrene.…”

“…Stronger anti-Candida albicans effect than chlorhexidine; mouth ulcer decrease and better healing compared to benzidamine [148] In vivo Cytotoxicity effect against lung cancer (H1299 cells) in animal model induced by benzopyrene Size: 170-200 nm; Sustained release; increase of bioavailability; expressive cell capture; greater reduction of H1299 cells viability [120] compared to free Cur…”