Controlled release and enhanced biological activity of chitosan-fabricated carbenoxolone nanoparticles

• Published in: International journal of biological macromolecules 2020-12, Vol.164, p.45-52
• Main Authors: Bharathala, Subhashini, Singh, Rajni, Sharma, Pankaj
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - pharmacology; Antimicrobial; Candida albicans - drug effects; Carbenoxolone; Carbenoxolone - chemistry; Carbenoxolone - pharmacology; Carbenoxolone - toxicity; Cell Line, Tumor; Chitosan - chemistry; Chitosan - pharmacology; Chitosan - toxicity; Controlled drug delivery; Cytotoxicity; Drug Carriers; Drug Liberation; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Hydrogen-Ion Concentration; Materials Testing; Microbial Sensitivity Tests; Nanochitosan; Nanoparticles - chemistry; Nanoparticles - toxicity; Spectroscopy, Fourier Transform Infrared; Static Electricity
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.07.086

Nanotechnology based antimicrobial drugs are developed to enhance their properties to combat multidrug resistant microbes. Carbenoxolone (CBX) is a semi-synthetic derivate of a natural substance from the licorice plant, with anti- (inflammatory, fungal, viral, microbial, fibrotic and cancer) properties. Though used to treat gastric ulcers, its low aqueous stability, low bioavailability and toxicity limited the drug's utility. To enhance its antimicrobial activity and reduce cytotoxicity, a controlled release nanoformulation was developed using natural biodegradable polymer chitosan (CS) as a carrier which is biocompatible, nontoxic with placid antimicrobial property. UV–visible spectroscopy, electron microscopy, and Fourier transform infrared spectroscopy were used for characterization of the resultant CS-CBX nanoparticles (NPs). They were spherical with uniform dispersion, ~200 nm in size with surface charge of +18.6 mV and drug encapsulation of >80%. Drug release kinetics exhibited a controlled release of 86% over 36 h following zero order kinetics. The anti-microbial activity against common pathogenic Gram −ve and +ve bacteria and yeast increased ~2-fold with a concomitant 4-fold reduction in cytotoxicity assessed using human lung adeno carcinoma (A549) cells. This study demonstrates the affirmative aspects of CS-CBX NPs as a promising antibacterial agent and may facilitate repositioning of the drug for diverse applications. •Carbexonolone (CBX) formulation using biodegradable chitosan (CS) as nanocarrier•Controlled drug release at pH 7.4, CS-CBX NPs stable for 3 months•Exhibit 2-fold higher antimicrobial activity; ~ 4-fold less cytotoxic•Free funcional group makes it tunable for specific applications