Medicinal Chemistry

Preparation and Characterization of Folate Conjugated Nanoparticles of Doxorubicin using PLGA-PEG-FOL Polymer

Abstract

Sai HS. Boddu, R. Vaishya, J. Jwala, A. Vadlapudi, D. Pal and A.K. Mitra

Purpose: This article describes the preparation and characterization of folate conjugated nanoparticles using poly(lactide-co-glycolide)-poly(ethylene glycol)-folate (PLGA-PEG-FOL) polymer for targeted delivery of anticancer agents. Methods: PLGA-PEG-FOL was synthesized by coupling di-block copolymer (PLGA-PEG-NH2) with folic acid. PLGA-PEG-FOL polymer was characterized by 1H NMR, GPC and FTIR. PLGA-PEG-FOL polymer was employed in the preparation of doxorubicin (DOX) loaded nanoparticles by double emulsion solvent evaporation (DESE), single emulsion solvent evaporation (SESE) and dialysis methods. Nanoparticles were characterized for size, morphology, entrapment efficiency, in vitro release and folate content. The presence of folate on nanoparticle surface was also confirmed using transmission electron microscopy. Qualitative uptake and cell viability studies were carried out in FOL receptor-positive ovarian cancer cells (SKOV3).
Results: DESE and SESE methods resulted in folate conjugated nanoparticles with an average size of 200 nm and entrapment efficiencies of 24.5 and 51.9% respectively. However, dialysis method resulted in microparticles with an average size of 2.5 μm. Folate conjugated nanoparticles exhibited higher uptake and cytotoxicity in SKOV3 cells in comparison with the pure DOX and unmodified nanoparticles.
Conclusion: PLGA-PEG-FOL can be utilized in the preparation of surface modified nanoparticles for targeted
delivery of anticancer agents to FOL-receptor-positive cancer cells.