Development of Self assembled Poly Carboxylate Chitosan Nanoparticles and their Application in Drug delivery

Abstract

Chitosan NPs were prepared by cross-linking with negatively charged carboxylic groups. Itaconic acid (CSPIA), Citraconic acid (CSCCA) and Crotonic acid (CSCA). The study includes optimization of reaction parameters for the synthesis of nanoparticles (NPs) using the statistical tool Taguchi, structural and surface characterization, thermal stability and cytotoxicity of the three synthesized Polycarboxylated chitosan NPs and their anti-cancer drug (docetaxel (DTX)) and anti-hyperlipidemic drug (Fenofibrate (FEB)) loaded counterparts. Further adsorption and release kinetics of drugs, thermodynamic and quantum mechanical studies have been carried out. The quantum study had revealed the interaction between the chitosan and the carboxylic acids. In reaction with IA, polymerization of IA takes place, followed by amide/ester linkages with CS. Whereas, with CCA and CA, the addition of amino group to double bond of the acids followed by the cross-linking to CS through amide/ester linkages. The results were confirmed with FT-IR analysis. SEM analysis revealed the rod-like structure and porous surface of the NPs. EDS analysis was an evidence for the grafting of polycarboxylic acids onto the chitosan chain. Cytotoxicity analysis had revealed that the plain NPs were compatible and non-toxic. It also confirmed that the NPs itself had some toxic activity against only on cancer cell lines. Percentage of DTX loading was comparatively high for PIA. The order was PIAgtPCAgtPCCA. For FEB, all the three carriers showed the similar percentage of loading. The FT-IR spectrum of the plain and drug loaded nanoparticle revealed the absence of new chemical bonding and presence of weak interactions; it may be hydrogen bond, Vander Waals forces or electrostatic interaction. The activation energy for all the drug and nanoparticle combinations lies within the range (5-40 KJ/mol) of physisorption. All the drug loading kinetics followed pseudo-second-order rate equation. Both the drugs showed a prolonged and sustained release from all the NPs