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Modification of Three-Phase Drug Release Mode of Octreotide PLGA Microspheres by Microsphere-Gel Composite System

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Abstract

In order to obtain sustained release of biodegradable microspheres, the purpose of this study was to design and characterize an injectable octreotide microsphere-gel composite system. The octreotide microspheres were prepared by phase separation method, which used PLGA as a carrier material, dimethyl silicone oil as a phase separation reagent, and n-heptane-Span 80 as a hardener. In addition, we used poloxamer 407 (PL 407) and poloxamer 188 (PL 188) as the thermosensitive gel matrix material. The composite system was obtained by scattering octreotide microspheres in a poloxamer gel. In vitro data showed that the release time of the composite system could last for about 50 days. Because of the blocking and control actions of the poloxamer gel, the initial burst release was significantly reduced and the plateau phase was eliminated. Pharmacokinetic data showed that the burst release of the composite system was significantly less than that of the microspheres, i.e., Cmax1 was reduced by about half. From day 2 to day 50, higher plasma concentration levels and more stable drug release behavior were exhibited. In addition, the good biocompatibility of the composite system in vivo was also demonstrated by hematoxylin-eosin (HE) staining. Therefore, the octreotide microsphere-gel composite system will be a new direction for hydrophilic polypeptide/protein-loaded sustained release dosage forms with high pharmacological activity.

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Acknowledgements

The authors would like to thank the Yantai University School of Pharmacy and Shandong Luye Pharmaceutical Co., Ltd. for their support and assistance in the National Key Laboratory of Long-acting and Targeted Formulations.

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Authors and Affiliations

  1. School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery, System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, People’s Republic of China

    Tengteng Wang, Wei Zhong, Xiucheng Yang, Aiping Wang & Rongcai Liang

  2. School of Pharmacy, Jining Medical University, Jining, Shandong Province, People’s Republic of China

    Chunyan Zhang

  3. State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong Province, People’s Republic of China

    Xiucheng Yang & Aiping Wang

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  1. Tengteng Wang
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  2. Chunyan Zhang
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  3. Wei Zhong
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Correspondence to Rongcai Liang.

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Wang, T., Zhang, C., Zhong, W. et al. Modification of Three-Phase Drug Release Mode of Octreotide PLGA Microspheres by Microsphere-Gel Composite System. AAPS PharmSciTech 20, 228 (2019). https://doi.org/10.1208/s12249-019-1438-4

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