Preparation of Hydrophilic Albumin Microspheres Using Polymeric Dispersing Agents

A new method for preparing glutaraldehyde cross-linked human serum albumin microspheres has been developed. Important aspects of this method include addition of glutaraldehyde in the organic phase and use of concentrated solutions of hydrophobic polymers (polymethylmethacrylate) or hydrophilic polymers (polyoxyethylene-polyoxypropylene block copolymer) as dispersion media. Uniform, round, solid, 3-150-microns hydrophilic microspheres were readily prepared by this process. The average size of microspheres was a function of dispersion time and energy input. Surface properties were altered by chemical modification using either 2-aminoethanol or aminoacetic acid to quench residual aldehyde groups. Optical and scanning electron microscopy and electronic particle size characterization indicate that the process is versatile in producing solid microspheres in a wide size range. Albumin microspheres of this type are readily dispersed in aqueous media for injection, without the need for surfactants.