Formulation development, characterization, and evaluation of sorafenib-loaded PLGA-chitosan nanoparticles

Area of Science:

• Biomedical Engineering
• Materials Science
• Pharmacology

Background:

• Hepatocellular carcinoma (HCC) treatment faces challenges with conventional sorafenib formulations, including limited bioavailability and side effects.
• Development of targeted drug delivery systems is crucial for improving HCC therapy efficacy and patient outcomes.
• Polymeric nanoparticles offer potential for enhanced drug solubility, stability, and controlled release of chemotherapeutic agents like sorafenib.

Purpose of the Study:

• To develop and characterize environmentally friendly, biodegradable, and biocompatible polymeric nanoparticles encapsulating sorafenib for targeted HCC therapy.
• To evaluate the in vitro drug release kinetics and in vivo pharmacokinetic profile of the developed sorafenib-loaded nanoparticles.
• To assess the in vitro cytotoxicity of the nanoformulations against HepG2 cancer cell lines.

Main Methods:

• Sorafenib-loaded PLGA-chitosan nanoparticles were synthesized using the solvent evaporation technique with poloxamer 407 as a stabilizer.
• In vitro drug release was assessed using the dialysis bag diffusion method, observing a biphasic release pattern over 10 days.
• In vivo pharmacokinetic studies were conducted in rabbits using HPLC analysis, and in vitro cytotoxicity was evaluated via MTT assay on HepG2 cells.

Main Results:

• The synthesized sorafenib-loaded PLGA-chitosan nanoparticles exhibited a biphasic drug release profile with a sustained release over 10 days.
• In vivo studies in rabbits showed significantly enhanced pharmacokinetic parameters (AUC0-t, Cmax, MRT, Vd, half-life) and decreased clearance compared to commercial sorafenib (Nexavar®).
• In vitro cytotoxicity assays demonstrated the efficacy of the developed nanoformulations against HepG2 cell lines.

Conclusions:

• Environmentally friendly, biodegradable, and biocompatible polymeric nanoparticles of sorafenib were successfully developed.
• The nanoformulations exhibit favorable physicochemical properties, improved targeting potential, and prolonged drug release kinetics.
• The developed sorafenib nanoformulations represent a promising alternative to conventional sorafenib, offering improved pharmacokinetic profiles and therapeutic potential for hepatocellular carcinoma.