Investigation of uniform biomaterial-based microspheres with precisely controlled size and size distribution for development of advanced drug delivery systems

Uniform microspheres (MS) of biocompatible polymers were investigated for use as advanced drug delivery vehicles. Novel methods of fabricating the precision particles (i.e., precision particle fabrication (PPF) techniques) of biomaterials were developed utilizing mechanical, hydrodynamic, and electric forces, where the drug release kinetics could be accurately controlled without uncertainties resulting from uncontrolled size distribution of the MS.; Monodisperse MS of EC with two different polymer viscosities (4- and 45-cp) were fabricated by the PPF method. The drugs encapsulated in the EC MS tended to concentrate near the surface depending on their hydrophilicity. The 30- and 35-mum MS exhibited more even distribution of the drug than the larger ones and showed almost linear release during the first 24 h.; To fabricate uniform MS of a hydrophilic polymer, an electric force was utilized to separate the uniformly generated drops. Both direct and indirect drop charging were incorporated, resulting in coulombic repulsion among the drops. Because no surfactant was involved, the method became nontoxic. For chitosan and starch, the dry MS were obtained by solvent evaporation at a high temperature (140 ∼ 160°C). However, due to their degradation at such high temperature, the gelatin solution drops were gelled at a low temperature (0 ∼ 4°C).; Uniform gelatin MS (GMS) were crosslinked using glutaraldehyde solutions with different concentrations. An acidic drug was introduced to form polyion complex with GMS. As a result of glutaraldehyde concentration gradient in the MS, heterogeneous crosslinking seemed to exist. The amount of complexed drug near the surface decreased as the glutaraldehyde concentration increased. In situ study of the degradation profiles of the GMS with higher glutaraldehyde concentrations revealed faster erosion at the center than near the surface.; Uniform chitosan MS (CMS) were employed for precisely controlled delivery of acidic drug, where colon-specific delivery could be realized without any additive polymers or toxic process. For strong acidic drug, the smaller the CMS, the more drugs could be contained until the colonic site hence the better candidate for colon-specific delivery. Weak acidic drug preferred the larger CMS due to the smaller amount of release at the gastric fluid.