A Uniform Ultra-Small Microsphere/SAIB Hybrid Depot with Low Burst Release for Long-Term Continuous Drug Release

In the present study, a uniform ultra-small microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB depot) was designed to provide a long-term sustained release drug delivery system which not only reduced the burst release of an SAIB depot, but also eliminated the lag-time of PLGA microspheres.

Risperidone loaded m-SAIB depot (Ris-m-SAIB depot) was characterized by in vitro drug release, pharmacokinetics, in vivo degradation and biocompatibility, in comparison with risperidone loaded SAIB depot (Ris-SAIB depot).

Ris-m-SAIB depot showed a low burst release (0.64%) and a reduced in vitro drug release rate due to the encapsulation of most drug in microspheres. After intramuscular administration, the in vivo burst release of Ris-m-SAIB was significantly decreased, as reflected by the low Cmax/Cs(4-td) (approximately 30-fold reduction), in comparison with Ris-SAIB depot. From 4 to 78 days, Ris-m-SAIB depot showed a higher plasma drug level (1.55 ~ 16.30 ng/ml) with a steadier drug release profile compared with Ris-SAIB depot. Ris-m-SAIB depot degraded gradually with a degradation t1/2 of 54.6 days and exhibited good biocompatibility in vivo.

These results demonstrate the potential application of a uniform ultra-small microsphere/SAIB hybrid depot for continuously delivering small drug molecules for long periods of time without burst release.