EVALUATION OF THE DRUG DELIVERY POTENTIAL OF CHITOSAN NANOPARTICLES CARRYING DOXORUBICIN AND QUERCETIN USING MOLECULAR MODELLING
Chaitra K., Durai Ananda Kumar T., Subba Rao V. Madhupantula and Asha Srinivasan*
Chitosan nanoparticles offers a versatile biocompatible drug delivery system for several drugs. The interaction of nanoparticles with the drug molecules and the energy involved in the stabilization decides the efficiency of drug delivery systems. Molecular dynamic simulations provide the conformational stability analysis for the nanoparticles-drug complex. In our study the interaction between the chitosan nanoparticles and the drugs doxorubicin and quercetin is studied. The atomic level confirmational stability between chitosan nanoparticles and drugs was demonstrated by the hydrogen bonds and π-π stacking interactions. The polar score for doxorubicin (2.2347 kcal/mol) with chitosan nanoparticles, doxorubicin with quercetin loaded chitosan nanoparticles (2.12 kcal/mol), quercetin with chitosan nanoparticles (1.27 kcal/mol) and quercetin with doxorubicin loaded chitosan nanoparticles (3.79 kcal/mol) is suggestive of spontaneous interactions and the complex is more stable. Molecular docking studies of doxorubicin and quercetin on the three-dimensional structures of P-gp (PDB-IDs: 6A6M and 6A6N) revealed the mechanism for the improved bioavailability of doxorubicin by quercetin. Quercetin established interaction with P-gp occurred through Mg2+ ion and Ser485, which is essential for the transport. Overall, the computational analysis suggests that chitosan nanoparticle as a potential nanocarrier for doxorubicin, and can be used for drug delivery systems.
Keywords: Chitosan nanoparticles, Doxorubicin, Quercetin, Molecular dynamics simulation, P-glycoprotein.
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