Multimeric System of RGD-Grafted PMMA-Nanoparticles as a Targeted Drug- Delivery System for Paclitaxel

Abstract

Background: Polymer-based nanoparticles as drug-delivery systems offer new therapeutic opportunities. Among them, ligand-mediated targeting, which increases selectivity and efficacy, allows controllable drug delivery. The aim of the this research was to prepare and characterize poly(methyl methacrylate) (PMMA) nanoparticles grafted with the -Arginine, Glycine, Aspartic Acid (RGD)- peptide sequence as a promising smart drug delivery system for Paclitaxel (PTX), directed at the sites of integrin receptor overexpression.

Methods: Nanoparticles were characterized by FT-IR and Raman spectroscopy, dynamic light scattering, zeta potential and transmission electron microscopy.

Results: RGD-PMMA-PTX size distribution was 17.58 ± 7.45 nm with a zeta potential of -38.73 ± 5.62 mV. According to the boxLucas Model, PTX was incorporated into nanoparticles with an entrapment efficiency of 100% (evaluated by HPLC analysis). In vitro sustained release was determined, with the maximum release of 55% and 40% after 21 days at pH 5.3 and 7.4, respectively. The highest inhibition on cell proliferation was found with RGD-PMMA-PTX nanoparticles (90 %).

Conclusion: The obtained results showed that RGD-PMMA-PTX represents an attractive and suitable therapeutic approach for targeting overexpressed integrins in the cancer cells.

Keywords: PMMA nanoparticles; drug delivery systems; entrapment efficiency; pH-responsive nanoparticles; targeted multimeric-RGD; transmission electron microscopy.