Preparation of uniform-sized microspheres and microcapsules by a novel technique and their applications for drug delivery

摘要

Polymer microspheres and microcapsules have important applications in drug delivery system. In the applications, the control of size and size distribution of microspheres and microcapsules is necessary in order to improve the bio-availability and drug efficiency. However, it is difficult to obtain uniform microsphere and microcapsules by conventional mechanical stirring method, homogenization and sonification techniques. In this study, a novel process-Membrane Emulsification Process was developed to prepare biodegradable polymer microspheres and microcapsules with narrow size distribution. Polylactide (PLA) or polylactide-poly (ethylene glycol) (PELA) microsphere, microcapsule, and hydrophilic polysaccharide microsphere with uniform size were successfully obtained respectively from O/W, W/O/W and W/O emulsions by developing the membrane emulsification technique to different emulsion systems. In the O/W system, PLA or PELA organic solution was pressed through the hydrophilic pores of the membrane into the aqueous phase containing stabilizer, the uniform droplets can be formed by utilizing the high interfacial tension between PLA or PELA solution and the membrane, then uniform PLA or PELA particles can be obtained by removing the solvent. In the preparation of PLA or PELA microcapsule, the W/O primary emulsion was pressed through the membrane into outer aqueous phase to form W/O/W emulsion, and the protein drug was encapsulated in the inner water phase. For the chitosan system, chitosan aqueous phase was pressed through the hydrophobic membrane into the oil phase to form W/O emulsion, and then the chitosan droplet was solidified by chemical or physical crosslinking method. Microspheres and microcapsules with micron-size and sub-micron size were prepared by direct and rapid membrane emulsification techniques, respectively. The CV values (coefficient of variation) which represent size distribution of obtained microsphere were around 10% and 15%, respectively for direct and rapid membrane emulsification techniques. PLA microsphere and PELA microcapsule with uniform size were used as drug delivery carriers of protein drugs for injection administration route, size effect was studied. Chitosan microspheres were applied for oral administration. By taking advantage of the uniform size and structural features of chitosan microspheres, an efficient oral administration system for insulin delivery was developed.