Preparation of PLA-PEG Di block copolymer based micelle as nanocarrier for anti-obesity drug delivery system

Abstract

Obesity is a widespread metabolic condition that accounts for most life-threatening disorders. Obesity has reached pandemic proportions worldwide. The delivery of many orally administered anti-obesity drugs is quite challenging because of their poor water solubility status. Low solubility limits the drug dissolution rate, which ultimately results in low bioavailability. A number of methods have been suggested to enhance the water solubility of the drug, but with limited success. In this study, we designed a polymer micelle consisting of polylactic acid–polyethylene glycol (PLA-PEG) as a nanocarrier for anti-obesity drugs "fenofibrate" to evaluate its performance. The copolymer was synthesized using direct solution polycondensation of l-lactic acid and polyethylene glycol instead of conventional ring opening polymerization, and the fenofibrate-loaded polymeric micelles were prepared by the solvent evaporation technique. The series of PLA-PEG diblock copolymer micelles were characterized using FT-IR spectroscopy. The particle size and polydispersity index of the polymeric micelles and the drug-loaded polymeric micelles were analyzed using dynamic light scattering (DLS). Finally, the encapsulation efficiency, drug loading content, and drug release behavior at different pHs were investigated using UV-Vis spectrophotometry. The DLS data demonstrated that the size of the micelle increased from 168 nm to 249 nm while the drugs were loaded inside the hydrophobic micelles core. The drug loading percentage was 6.01 %, while the encapsulation efficiency was 48.16 %. Moreover, the release studies exhibited a clear pH-dependent drug release behavior. About 80% of the drugs were released from the micelle after 6 hours at a stomach pH of 1.2, whereas a slightly slower drug release was obtained at a blood pH of 7.4 and a significantly lower drug release was obtained at a mildly acidic intestine pH of 6.5. All of these findings suggest that PLA-PEG diblock copolymer micelle may be employed as a nanocarrier for orally delivered fenofibrate medicines in the future to improve water solubility and efficiency. Further research should be conducted on the behavior of PLA-PEG diblock copolymer micelles in vivo as well as their potential for drug targeting and clinical trials.