Biodegradable poly(D,L-lactide-co-glycolide)/poly(L-γ-glutamic acid) nanoparticles conjugated to folic acid for targeted delivery of doxorubicin

摘要

A novel targeted drug delivery nanoparticle system based on poly(D,L-lactide-co-glycolide) add (PLGA) for delivery of doxorubicin (DOX) was developed. DOX-PLGA NPs were obtained by the emulsification-solvent evaporation technique. Then, their surface was modified with poly(L-γ-glutamic acid) (γ-PGA) and finally conjugated to modified folic acid (FA) as a targeting ligand. The surface modification and FA conjugation were followed by UV-Vis and FT-IR spectroscopies. Morphology was observed by TEM/SEM. Particle size, PDI and zeta potential were measured using DLS studies. Encapsulation and loading efficiencies, and DOX release kinetics were determined. Specific uptake and cell viability of DOX-PLGA/γ-PGA-FA NPs were tested in HeLa cells. Quasi-spherical nanoparticles with a particle size lower than 600 nm (DLS) were obtained. Spectroscopic techniques demonstrated the successful surface modification with γ-PGA and FA conjugation. Release profile of DOX-PLGA/γ-PGA-FA NPs showed a release of 55.4 ± 0.6% after seven days, in an acidic environment. HeLa cells exhibited a decrease in viability when treated with DOX-PLGA/γ-PGA-AF NPs, and cellular uptake was attributed to FA receptor-mediated endocytosis. These results suggest that DOX-PLGA/γ-PGA-FA NPs are a potential targeted drug carrier for further applications in cancer therapy.