Biodegradable nanoparticles for local drug delivery

To reduce restenosis after balloon angioplasty, local drug administration has the intuitive appeal of a higher site-specificity with lower drug doses needed than in the case of systemic administration. Whereas free drug administered locally diffuses out within a couple of minutes after restoration of blood circulation [1,2], the use of nanoparticles as drug carriers increases the drug uptake and the residence time considerably. In the preparation of these nanoparticles, a stabilizer is usually employed. However, 90–95% of the stabilizer is washed away during purification, which may be a drawback when further surface modification is anticipated. To obtain biodegradable nanoparticles that allow further surface modification, particles were prepared from poly(ethylene oxide)-poly(DL-lactic-co-glycolic acid) (PEO-PLGA) block copolymers. In aqueous environment the hydrophilic PEO-block may serve as a stabilizer, whereas the PEO-endgroup offers possibilities for nanoparticle surface modification. Moreover, drug-loaded particles were prepared and the drug loading efficiency was determined. Probucol was chosen as a drug, as it has an anti-restenosis activity [3]. Since drug release from the nanoparticles takes place by diffusion from and degradation of the matrix, the in vitro degradation of the PEO-PLGA nanoparticles was studied. The in vitro characteristics of these particles were compared with conventionally stabilized poly(DL-lactic acid) (PDLLA) and PLGA nanoparticles.