Formation of PEG-PLGA Microspheres for Controlled Release of Simvastatin and Carvacrol: Enhanced Lipid-Lowering Efficacy and Improved Patient Compliance in Hyperlipidemia Therapy

Polymer-based drug-controlled release systems offer greater efficacy and potency than conventional therapies. However, prominent drug side effects, lower circulation, and low drug loading capabilities limit their application range. In this work, the combination of Simvastatin (SIV) and Carvacrol (CAV) into PEG-PLGA microspheres (SIV-CAV-PP-MS) was achieved via an emulsification-solvent evaporation technique, resulting in microspheres characterized by high encapsulation efficiency and reduced particle size. In vitro studies demonstrated that the cumulative drug release increased with higher SIV and CAV levels in the release medium, reaching 88.91% and 89.35% at 25 days. Pharmacokinetic analysis revealed that the concentrations of SIV and CAV reached their maximum levels at approximately seven days in the SIV-CAV-PP-MS group, which indicates that using PEG-PLGA as a carrier significantly delays drug release. In vivo, evaluation demonstrated that the SIV-CAV-PP-MS high-dose group and positive drug control group showed reductions in low-density lipoprotein cholesterol levels by 0.39-fold and 0.36-fold compared to the Hyperlipidemia model group, and the addition of CAV significantly enhanced the lipid-lowering effects of SIV. Histological examinations indicated that the SIV-CAV-PP-MS medium-dose group displayed histological features more closely resembling those of normal mice compared to the Simvastatin control group, with a well-organized hepatocyte structure, a significant reduction in lipids, and improved liver health. The prepared polymeric microsphere utilizing SIV and SAV will be a promising dosage form for hyperlipidemia disease patients, with superior lipid-lowering efficacy and improved patient compliance.