Abstract

The key to success of proteins as biopharmaceuticals is to have in place an efficient drug delivery system that allows in gaining access to their target sites. A novel procedure of preparing ovoalbumin-loaded Eudragit^® S100 microparticles, based on combining salting out and double emulsion-evaporation steps was developed. The ratio of a water miscible solvent (acetone and isopropanol) to a non-water-miscible solvent (chloroform) and salt addition to aqueous phase external were shown to be the primary determinants of size, polydispersity index (PI) and encapsulation efficiency (EE). Once optimized, using an organic phase of 3:0.5:1.5 (acetone:isopropanol:chloroform, v/v/v), further control was exerted using modification of acetone diffusion by alterations in MgCl₂ concentration. Diffusion control, using 75% w/w MgCl₂ solution, produced microparticles with a mean size of 26.3 µm, a good PI of 0.36 and 56.5 ± 0.5% EE. Electron microscopy showed the particles to be smooth and spherical. Ovoalbumin release studies using different buffers demonstrated immediate release in the buffer at alkaline pH. Calorimetry studies suggested that ovoalbumin existed in the microparticle as a molecular dispersion. Thus, Eudragit^® S100 microparticles have great potential as oral carriers for delivery of proteins to the intestines.

Key words: Double emulsion/solvent evaporation, emulsification-diffusion, microparticles, protein encapsulation. 

Abbreviation

MP: Polymeric microparticles, PI: polydispersity index, PVA: poly(vinyl-alcohol), OA: ovoalbumin, IAP: inner aqueous phase, AC: acetone, OP: organic phase, CH: chloroform, EPA: external aqueous phase, ISP: isopropanol, SEM: scanning electronic microscopy, EE: entrapment efficiency.