Reservoir-Type Microcapsules Prepared by the Solvent Exchange Method: Effect of Formulation Parameters on Microencapsulation of Lysozyme (original) (raw)

2006, Molecular Pharmaceutics

A new microencapsulation technique based on the solvent exchange method was implemented using an ultrasonic atomizer system to encapsulate a protein drug in mild conditions. The reservoir-type microcapsules encapsulating lysozyme as a model protein were prepared by inducing collisions between the aqueous droplets containing lysozyme and the droplets of organic solvent with dissolved poly(lactic acid-co-glycolic acid) (PLGA).The main focus of the study was to examine formulation variables on the size and the encapsulation efficiency of the formed microcapsules. The formulation variables examined were concentrations of mannose in the aqueous cores, NaCl in the aqueous collection medium, and PLGA in organic solvent. The mean diameter of the microcapsules ranged from 40 µm to 100 µm. Smaller microcapsules showed lower encapsulation efficiencies. The resulting microcapsules released native lysozyme in a sustained manner, and the release rate was dependent on the formulation conditions, such as the concentration and molecular weight of the polymer used. The solvent exchange method does not induce lysozyme aggregation and loss of its biological activity. The solvent exchange method, implemented by the ultrasonic atomizer system, provides an effective tool to prepare reservoir-type microcapsules for delivering proteins. . † Present address: Department of Advanced Polymer and Fiber Materials, Kyung Hee University, Gyeonggi-do 449-701, South Korea. (1) Bartus, R. T.; Tracy, M. A.; Emerich, D. F.; Zale, S. E. Sustained delivery of proteins for novel therapeutic agents. Science 1998, 281, 1161-1162. (2) Sinha, V. R.; Trehan, A. Biodegradable microspheres for protein delivery. J. Controlled Release 2003, 90, 261-280. (3) Tamber, H.; Johansen, P.; Merkle, H. P.; Gander, B. Formulation aspects of biodegradable polymeric microspheres for antigen delivery.