RESUMEN
Investigation of the influence of molecular weight of polycaprolactone on: Particle size and particle size distribution of microparticles prepared by W/O/W multiple .emulsions solvent evaporation/extraction method, Stability of protein loaded in these microparticles, morphology and surface state of microparticles, encapsulation efficiency and Percentage of burst release. A W/O/W multiple emulsions solvent evaporation/extraction method was modified to prepare protein-loaded microparticles. Methemoglobin was used as a model protein. Low and high molecular weights of polycaprolactone-the hyrophob, biodegradable and biocompatible polymer-were used to encapsulate the protein. Dichiorometane-a solvent that is immiscible with water-was used as a polymer solvent. Polyvinyl alcohol was used as a stabilizer in the outer aqueous phase. High encapsulation efficiency values, low burst release, preservation of protein native conformation and multilayered microcapsules were obtained, either by using polycaprolactone [PCL] 14.000 alone or by using PCL 14.0000 with PCL 65.000. PCL 14.000 was not solved with PCL 65.000 in the same solution. Organic phases were divided into solutions with different concentrations and/or different molecular weights. Concentrations of organic phase solutions were above polycaprolactone cloud point and low temperatures were used to prepare primary and secondary emulsions. Non porous microcapsules were obtained when low molecular weight of polymer was used alone, while closed pores were noticed on the surface of microcapsules prepared by using high and low molecular weights together. The layers of low molecular weight of polycaprolactone covered the pores of high molecular weight layers. Low burst release values were attributed to non porous microstructures of microcapsules as well as to reduction of protein quantities on the surface of microcapsules. Fabrication of microcapsules by using high and low molecular weights of polycaprolactone together instead of using low molecular weight alone resulted in burst release reduction from 12.8% to 9.6% and reduction of encapsulation efficiency values from 97.4% to 88.17%. Protein native conformation was preserved in both cases. A novel method was developed to fabricate multilayered and non porous microcapsules-either by using low molecular weight of polycaprolactone alone or by using low and high molecular weights of polycaprolactone together-by modifying W/O/W multiple emulsions solvent evaporation/extraction method. Method modifications and formuJation factors were behind preservation of protein tertiary structure and obtaining high encapsulation efficiency values which reached 97.4%. The low burst effect was reduced from 12.8% to 9.6% by using high and low molecular weights of polycaprolactone together instead of using low molecular weight alone. Solving the problem of porous structure of microcapsules-accompanied with the addition of high molecular weight of polycaprolactone to low molecular weight-may play a significant role in reducing burst release due to the longer period required for the degradation of higher molecular weight of polymer