Controlled release of proteins from poly(L‐lactic acid) coated polyisobutylcyanoacrylate microcapsules

Poly(L‐lactic acid)‐coated polyisobutylcyanoacrylate microcapsules containing protein molecules were prepared by a single‐step procedure based on either a double‐emulsion‐solvent evaporation method or a spray‐drying method. First, an aqueous protein solution was emulsified in an organic phase of methylene chloride containing a wall‐forming monomer (isobutylcyanoacrylate), various kinds of poly(L‐lactic acid), and a surfactant. An immediate polymerization process of isobutylcyanoacrylate takes place at the W/O interface upon contact with hydroxide ion in the aqueous phase, leading to the formation of a polyisobutylcyanoacrylate wall around the aqueous droplets. This W/O emulsion was reemulsified in an aqueous solution to promote the solvent removal and, consequently, the precipitation of poly(L‐lactic acid) onto polyisobutylcyanoacrylate microcapsules or was spraydried to directly deposit the poly(L‐lactic acid) on the wall. Three proteins, bovine serum albumin, horseradish peroxidase, and tetanus toxoid, were encapsulated in these poly(L‐lactic acid)‐coated polyisobutylcyanoacrylate microcapsules, and then their release profiles were examined in vitro as a function of molecular weight of poly(L‐lactic acid) and its copolymers with glycolic acid. These formulations exhibited a low “burst” effect at initial incubation stages and released the proteins for extended periods of time. Subcutaneous injections of the tetanus toxoid‐loaded microparticles into rats showed that the time course of immunization (antibody titer) can be controlled by the type of polymer matrices used. © 1994 John Wiley & Sons, Inc.