Modeling of Chitosan modified PLGA atorvastatin-curcumin conjugate (AT-CU) nanoparticles, overcoming the barriers associated with PLGA: an approach for better management of atherosclerosis.

Conjugate drugs are evolving into potent techniques in the drug development process for enhancing the biopharmaceutical, physicochemical, and pharmacokinetic properties. Atorvastatin (AT) is the first line of treatment for coronary atherosclerosis; however its therapeutic efficacy is limited because of its poor solubility and fast pass metabolism. Curcumin (CU) is evidenced in several crucial signaling pathways linked to lipid regulation and inflammation. To enhance the therapeutic efficacy and physical properties of AT and CU, a new conjugate derivative (AT-CU) was synthesized and assessed by in silico, in vitro characterizations, and in vivo efficacy through mice model. Although the biocompatibility and biodegradability of Polylactic-co-Glycolic Acid (PLGA) in nanoparticles are well documented, burst release is a common issue with this polymer. Hence the current work used chitosan as a drug release modifier to the PLGA nanoparticles. The chitosan-modified PLGA AT-CU nanoparticles were prepaid by single emulsion and solvent evaporation technique. With raising the concentration of chitosan the particle size grew from 139.2 nm to 197.7 nm, the zeta potential rose from -20.57 mV to 28.32 mV, and the drug encapsulation efficiency improved from 71.81 % to 90.57 %. At 18 hours, the burst release of AT-CU from PLGA nanoparticles was seen, hitting abruptly 70.8%. For chitosan-modified PLGA nanoparticles, the burst release pattern was significantly reduced which could be due to the adsorption of the drug on the surface of chitosan. The efficiency of the ideal formulation i.e F4 (chitosan/PLGA= 0.4) in treating atherosclerosis was further strongly evidenced by in vivo investigation.