Carrageenan-stabilized chitosan alginate nanoparticles loaded with ethionamide for the treatment of tuberculosis

Abstract

The objective of this work was to prepare ethionamide-loaded, cross linker free, chitosan alginate nanoparticles stabilized with varying amounts of carrageenan using simple inotropic gelation. The nanoparticles formulation was manipulated to optimize drug loading and release. Three different formulations containing different percentages of carrageenan (0%, 42%, and 59%) were evaluated for particles size, zeta potential, entrapment, and release. Results showed that carrageenan enhanced the stability of the nanoparticles to the formulation process and enhanced the entrapment of ethionamide in the nanoparticles (0.36 μg/mg for 0% carrageenan formulation vs 3.1 μg/mg for 59% carrageenan formulation). Moreover, nanoparticles exhibited controlled release over 96 h and the release was reduced with increasing the carrageenan content. The nanoparticles size for all formulations was found to in the range of 300 nm. These results were found concurring in size with the results obtained from TEM. Furthermore, the DSC and FTIR evaluation of the ethionamide in the freeze-dried nanoparticle preparation showed no chemical interaction between ethionamide nanocrystals and the excipients. Additionally, the ethionamide loaded nanoparticles showed significant antimycobacterial activity against H37RA mycobacterium strain using resazurin microtiter assay (REMA). Thus, it can inferred from these results that our nanoparticle formulations have a great potential in the treatment of tuberculosis.