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 hydrophobic molecule, was incorporated in the core with loadings varying from about 7 to 32% (w/w) and increasing with the particle size. Particles with sizes from about 250 to 820 nm and low polydispersity were prepared with good reproducibility; the polymer concentration (at constant surfactant concentration) governed the particle size. The large particles with a high loading ( approximately 30%) showed under in vitro conditions a slow release over 24-30 h, the medium sized carriers (loading of approximately 13%) released the drug over about 15 h, whereas the small particles with small loading ( approximately 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 the drug incorporated in the polymer matrix.