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

作者：Lin, Xia^*; Xu, Yuhong; Tang, Xing; Zhang, Yan; Chen, Jian; Zhang, Yu; He, Haibing; Yang, Ziyi

来源：Pharmaceutical Research, 2015, 32(11): 3708-3721.

DOI：10.1007/s11095-015-1731-1

• uniformultra-small microsphere/SAIB hybrid depot
• burst release
• continuous drug release
• degradation in vivo
• biocompatibility

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 C-max/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 similar to 16.30 ng/ml) with a steadier drug release profile compared with Ris-SAIB depot. Ris-m-SAIB depot degraded gradually with a degradation t(1/2) 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.

• 出版日期2015-11
• 单位沈阳药科大学; 江南大学; 上海交通大学; 沈阳大学