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 (similar to 30%) showed under in vitro conditions a slow release over 24-30 h, the medium sized carriers (loading of similar to 13%) released the drug 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 the drug incorporated in the polymer matrix. (C) 1999 Elsevier Science B.V. All rights reserved.