The microencapsulation of protein using a novel ternary blend based on poly(a-caprolactone)

Abstract

Microspheres with an entrapped protein were prepared from poly(e-caprolac-tone) (PCL), and a novel ternary blend, comprising of high and low molecular weight PCL in combination with poloxamer 181, a triblock copolymer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide). The inclusion of low molecular weight PCL served to enhance phase mixing by a reduction in the molecular weight of the polymeric components. Encapsulation of the protein, bovine serum albumin, was possible using a water-in-oil-in-water multiple emulsion solvent evaporation technique. Microspheres prepared from unblended PCL were irregular and porous in nature. The presence of surface imperfections and macroscopic pores was attributable to the high rate of crystallization of the PCL polymer from solution. The inclusion of poloxamer 181 into the matrix retarded the rate of crystallization of the PCL, thereby enhancing particulate sphericity and regularity. Manipulation of the process parameters of blended microspheres provided a means of controlling the particle size and the entrapment efficiency of the protein. The influence of variables such as protein to polymer ratio, internal phase volume and emulsifier concentration in both the internal and external aqueous phases, on the properties of the microspheres was investigated. A mean particle size ranging from 10 to 42 μm could be achieved by altering the internal phase volume of the primary emulsion, whilst a high protein entrapment (11% w/w) was possible with a protein to polymer ratio of 1:4. Native-PAGE analysis of the entrapped protein indicated a maintenance of bulk structural integrity.

Key Words:

• Poly(caprolactone) ternary blend
• biodegradable microspheres
• protein delivery
• bovine serum albumin
• solvent evaporation