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 bio-pharmaceutical, 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 de-rivative (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 nano -particles 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 h, 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.

Automated summary

Conjugate drugs are being widely studied for their potential in improving the properties of drugs. A new conjugate derivative (AT-CU) of atorvastatin and curcumin was synthesized and evaluated in terms of its physical and therapeutic properties. Chitosan-modified PLGA nanoparticles were prepared and showed improved drug encapsulation efficiency and reduced burst release. In vivo studies further confirmed the effectiveness of the ideal formulation in treating atherosclerosis.