Xia Lin1,2, Yuhong Xu3, Xing Tang4, Yan Zhang5, Jian Chen3, Yu Zhang4, Haibing He4, Ziyi Yang6. 1. School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China. 13840485982@163.com. 2. School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, People's Republic of China. 13840485982@163.com. 3. School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China. 4. Department of Pharmaceutics Science, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China. 5. Normal College, Shenyang University, Shenyang, 110044, People's Republic of China. 6. School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, People's Republic of China. ziggyyang@163.com.
Abstract
PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: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). RESULTS: 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. CONCLUSION: 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.
Entities:
Keywords:
biocompatibility; burst release; continuous drug release; degradation in vivo; uniform ultra-small microsphere/SAIB hybrid depot