A novel targeted drug delivery nanoparticle system based on poly(D,L-lactide-co-glycolide) acid (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 600nm (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.
With the thorough comprehension of biological effects depending on structure, it is possible to design specific systems for specific diseases, treatments and patients. The ability of polymer- based nanoparticles to modify and improve pharmacokinetics and pharmacodynamics, associated to techniques for enhancement of the therapeutic efficiency with minimal side effects, demonstrate the advantages of these systems.
The obtained results showed that RGD-PMMA-PTX represents an attractive and suitable therapeutic approach for targeting overexpressed integrins in the cancer cells.
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