Preparation of silk fibroin microspheres by emulsificationdiffusion method for controlled release drug delivery applications

Abstract

Silk fibroin (SF) microspheres containing a model drug were prepared by a simple water-in-oil emulsification-diffusion method. Aqueous SF solution and ethyl acetate were used as water and oil phases, respectively. Methylene Blue was used as a water-soluble model drug. Effect of drug content on microsphere characteristics, drug loading efficiency and drug release behavior was determined. Scanning electron microscopy revealed that drug-loaded SF microspheres were spherical in shape with a smooth surface. The SF microspheres showed predominant random coil SF conformation. All drug loading efficiencies were approximately 50%. An increase in drug/SF ratio could lead to an increase in %drug release and surface erosion after the drug release test. Drug release from SF microspheres is due to SF matrix swelling and surface erosion processes.

Biodegradable silk fibroin/chitosan blend microparticles prepared by emulsification-diffusion method

“…This method has been successfully used to prepare both SF (23,24,35) and CS (36) microparticles. For this method, the aqueous SF/CS blend solution was emulsified as dispersed droplets in the ethyl acetate continuous phase before solidification during the diffusion of water and ethyl acetate, as previously described in our work (38).…”

“…The rough surface texture of the last two microparticles was formed because the surface regions of the droplets were the first to dry and solidify, forming a skin that shriveled when the interior regions dried out. For the W/O emulsion solvent diffusion method used in our study, the irregular shape of the SF microparticles may form due to the rapid solidification of the SF droplet surface regions during the solvent diffusion process (23,24,35). However, the CS microparticles and SF/CS blend microparticles were nearly spherical in shape ( Figure 1B-E).…”

“…The porous structure could form when a small amount of non-solvent (ethyl acetate) diffused into each emulsion droplet and reduced the solubility of the SF and CS, which then solidified and precipitated. The porous microparticles may have been formed due to the phase separation within the water 1 -in-oil-in-water 2 double emulsion droplets before solidification (24,36,40). However, the internal porous structures were completely covered with continuous particle surfaces.…”

“…The external continuous phase, ethyl acetate, can more easily diffuse into the dispersed droplets of the SF solution than into those of the CS solution. The diffused ethyl acetate induced a porous structure within the microparticles after solidification and drying (24).…”

“…Many researchers have reported the formation of plain SF microparticles by diverse methods including spraydrying (19,20), lipid vesicle templates (21), water-in-oil (W/O) emulsion solvent evaporation (22), W/O emulsion solvent diffusion (23,24), phase separation of SF/polyvinyl alcohol blend films (25) and salting out (4). The dissolution of SF matrix has been modified and controlled via the use of a cross-linker, alcohol, heat treatments and by blending with hydrophilic polymers for drug delivery applications.…”