CONTROLLED RELEASE OF PROTEIN DRUG FROM POLY(ORTHO-ESTERS) MICROSPHERES

Self catalysed and latent acid poly(ortho esters) (POEs) with different compositions were used to fabricate the microspheres using a W/O/W double emulsion solvent extraction/evaporation method. The characteristics of POEs microspheres were analyzed by size distribution, surface morphology, protein encapsulation efficiency, initial burst and release profile. The results showed that protein-containing microspheres fabricated with different compositions of POEs had different release profiles. For instance, compared with the microspheres of POE prepared from 3, 9-diethylidene – 2, 4, 8, 10 – tetraoxaspiro [5, 5] undecane, a 89/10/1 mixture of cyclohexanedimethanol (CDM), triethyleneglycol (TEG) and cyclohexanedimethanol – monolactate (CDM-mLT) (POE4), the microspheres of POE prepared from a 75/20/5 mixture of CDM, TEG and CDM-mLT (POE3) has a more rapid release rate. It is due to this fact that TEG is more hydrophilic, compared with CDM. So a higher concentration of TEG dimer segments in the POE3 backbone can result in a faster water penetration rate. As a consequence, the degradation rate of POE3 is faster than that of POE4. However, the segments of hexanediol-diglycolate (HD-diGL) are more hydrophilic than CDM-mLT. So the release rate of the microspheres of POE prepared from 3, 9-diethylidene – 2, 4, 8, 10 – tetraoxaspiro [5, 5] undecane, a 75/20/5 mixture of CDM, TEG and HD-diGL (POE2) is faster than that of POE3. Moreover, POE microspheres at 37°C has a higher release rate than at 22°C. The SEM images of POE microspheres showed that all the POE microspheres have smooth and non-pores surface morphology, resulting in a low initial release. We suggest that poly (orthoesters) can be utilized for microencapsulation of active agents such as protein drugs. By using POEs with various compositions, release profiles of protein drug and the polymer degradation rate can be controlled.