Preparation and characterization of protein-loaded poly (e-caprolactone ) microparticles: application to some biopharmaceuticals

The advent of genetic engineering has resulted in proliferation of new biopharmaceuticals that are orally inactive and must be administered by subcutaneous injection or intravenous infusion. Among different approaches, microencapsulation have received increasing attention in the design and delivery of peptides and proteins the last ten years. But to our knowledge none of these entrapment methods make use of pure poly(ε-caprolactone) (PCL) as polymeric matrix. The purpose of this work was to efficiently entrap in PCL microparticles some biopharmaceuticals used either in immunization (bovine serum albumin, BSA, a model antigen and muramyl dipeptide, MDP, an adjuvant for immunization) or in therapy (superoxide dismutase, SOD) using solvent evaporation method.
Using the (cater-in oil)-in water emulsion solvent evaporation method, smooth and spherical pure PCL microparticles with high entrapment efficiency (50.29 ± 5.01%) were prepared. The release profiles of BSA in the two release media were significantly different and faster in presence of sodium dodecyl sulphate. Moreover they exhibited a relatively low burst effect after 24 hours (<30%) followed by a continuous release over six months. The process of manufacturing produced a high entrapment efficiency of MDP (63.58 ± 0.40%) without altering its integrity as shown by chromatogram peaks analysis of α and β anomers. Moreover the co-entrapment of NMP+BSA increased MDP entrapment efficiency. These microparticles were resistant to simulated gastric fluid and found application in design of oral vaccine against schistosomiasis.
Using the same method, however a high entrapment efficiency of SOD was achieved (~60%) significant enzyme activity loss occurred (percentage retained biological activity ~ 8%). This was ascribed to the deleterious effect of the polymer solvent. To overcome this problem the reversed micelle solvent evaporation method was used leading to an entrapment efficiency of 47.4% and a percentage retained biological activity >90%. The 24-hours burst release of SOD increased with the concentration of the sucrose ester initially used in the formulation. After that, no considerable influence of this parameter was noticed. The enzyme was released in its stable and active form in a controlled manner over at least 72 hours. Such formulation could find potential application in the treatment of some chronic inflammatory diseases if future investigation were conclusive.
In addition to its numerous desirable properties, PCL appears to be a potential alternative for continuous delivery of some biopharmaceuticals