Lidocaine-loaded biodegradable nanospheres. I. Optimization of the drug incorporation into the polymer matrix

Spherical nanoparticulate drug carriers made of poly(D,L-lactic acid) with controlled size were designed. A local anesthetic, lidocaine, a small hydro phobic molecule, was incorporated in the core with loadings varying from ab out 7 to 32% (w/w) and increasing with the particle size. Particles with si zes from about 250 to 820 nm and low polydispersity were prepared with good reproducibility; the polymer concentration (at constant surfactant concent ration) governed the particle size. The large particles with a high loading (similar to 30%) showed under in vitro conditions a slow release over 24-3 0 h, the medium sized carriers (loading of similar to 13%) released the dru g over about 15 h, whereas the small particles with small loading (similar to 7%) exhibited a rapid release over a couple of hours. It seems that the drug release rate is related to the state (crystallized or dispersed) of th e drug incorporated in the polymer matrix. (C) 1999 Elsevier Science B.V. A ll rights reserved.