In cancer, therapeutic alternatives include the use of antineoplastic drugs; however, current drugs lack selectivity for only to damaged tissue, which produce severe adverse effects. Improvements in the development of... [ view full abstract ]
In cancer, therapeutic alternatives include the use of antineoplastic drugs; however, current drugs lack selectivity for only to damaged tissue, which produce severe adverse effects. Improvements in the development of polymer-based nanoparticles as drug-delivery systems, offers new therapeutic opportunities. Among them, ligand-mediated targeting, interacts with specific receptors on target cells, increases selectivity and efficacy and allows controllable drug delivery, increasing therapeutic benefits, while minimizing side effects. Additionally, it offers the possibilities of encapsulating poorly-soluble drugs, protecting therapeutic molecules, and modifying the pharmacokinetic profile of nanoparticle-incorporated drugs.
The aim of this research was to prepare and to 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 to sites with integrin receptor overexpression, such as angiogenesis sites in some solid tumors.
Characterization techniques included FT-IR spectroscopy, particle size by dynamic light scattering (DLS), zeta potential, morphology by transmission electron microscopy (TEM), entrapment efficiency (%EE), drug release profile and cytotoxicity in positive integrin receptor C6 cell line. The vibrational spectroscopy characterization indicated the formation of the PMMA polymer, PMMA-PTX or RGD-PMMA-PTX modified polymer. RGD-PMMA-PTX size distribution was found to be 17.58 ± 7.45 nm with a zeta potential of
-38.73 ± 5.62 mV and of spheroidal form. According to the boxLucas Model, PTX was incorporated into polymeric matrix with an entrapment efficiency maximum of 100% (HPLC). These nanoparticles showed sustained in vitro release with maximum release percentages of 55% and 40% after 21 days at pH 5.3 and 7.4, respectively, a relatively fast release of PTX in the first 5 hours at pH 5.3, but not for pH 7.4 attributable to the diffusion and dissolution of PTX that was entrapped superficially in the polymer matrix. RGD-PMMA-PTX nanoparticles were shown to be more cytotoxic to C6 glioblastoma cells than non-targeted nanoparticles and free PTX.
These results indicate that RGD-PMMA-PTX is suitable for specific PTX delivery in cells that over-express ανβ3 receptors in processes of angiogenesis. In this study, the small amount of PTX required to produce an anti-proliferative effect opens the possibility of reducing side effects.
Targeted drug delivery and Nanocarriers , Nanomedecine for cancer diagnosis & therapy
