New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles.

Local delivery of antiproliferative drugs encapsulated in biodegradable nanoparticles has shown promise as an experimental strategy for preventing vascular restenosis development. The general aim of this work was to develop polymeric nanoparticle carriers with bioadhesive properties, and to evaluate its adjuvant potential for local, intramural delivery of rapamycin for inhibition of restenosis. The bioadhesive rapamycin-loaded PLGA nanoparticles were obtained by applying carbopol 940 of different concentrations as stabilizer and bioadhesive agent. The resultant nanoparticles were characterized concerning physicochemical properties such as morphology, particle size, zeta potential, entrapment efficiency, drug loading, drug release in vitro, stability in vitro as well as the arterial uptake and retention ability in an ex-vivo model. The results revealed that carbopol could serve as a better stabilizer in the preparation of rapamycin-loaded PLGA nanoparticles compared with PVA, and the physicochemical characteristics of the obtained PLGA nanoparticles were affected by the concentration of carbopol. Furthermore, it was found that carbopol could impart the nanoparticles with bioadhesive properties, improving the rentention and uptake of nanoparticles in the arterial wall, benefiting the nanoparticles for efficient localization of therapeutic agents in restenosis site. Cell viability assay results showed that blank PLGA-carbopol nanoparticles exhibited low toxicity and excellent biocompatibility and rapamycin-loaded nanoparticles with a smaller particle size (< 200 nm) had an increased antiproliferative effect on cells in comparison to free drug. These results indicated that this research might provide a potential experimental basis for the further study of carbopol stabilized bioadhesive nanoparticles against restenosis in vivo.