Development of polymethacrylic/poloxamer microparticles for topical administration of biotech drugs

The aim of this study was to produce biocompatibile microparticles for the mucosal administration of aminoacid based molecules. As aminoacid based molecules, two biotech drugs, namely BPTI (bovine pancreatic trypsin inhibitor) and DTK, a 15 aminoacids sequence derived from HSV-1 glycoprotein B, were employed. Microparticles were prepared using a blend of polymethacrylic polymer and poloxamer 407 in a weight ratio of 50:30:20. A water-in-oil-in-water double emulsion method was employed. As dispersing phase a PVA solution (2.5% w/w) was used. Microparticles size, polydispersity and morphology were investigated by optical and scanning electron microscopy observations. The loading efficiency of drugs within microparticles was determined by double monochromator spectrophotometer for BPTI and by HPLC for DTK. In vitro drug release profile was obtained by dialysis method using acetate buffer as receiving buffer. The amount of BPTI and DTK released was quantified by HPLC analyses using respectively a gel filtration or an inverse phase column. After the incorporation of both biotech drugs, the obtained microparticles maintained a round shape and a narrow size distribution. Particularly, microparticles showed a mean size of 8.56 µm ± 7.9 and of 7.24 µm ± 6.2 for BPTI and DTK, respectively. Nevertheless, the entrapment efficiency was 67.5% in the case of BPTI and 79.7% in the case DTK. The in vitro studies showed that the release of biotech drugs from microparticles was slower with respect to that of the corresponding control solutions. In particular, the release of DTK began after the fifth hour and after the first hour for BPTI, reaching after 24 h a release of 20.6% for DTK and of 42.1% for BPTI. The present study suggests that these polymethacrylic/poloxamer microparticles, characterized by a slow and prolonged release, could be a feasible strategy to topically deliver proteins and peptides.