期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 144, 期 -, 页码 217-229出版社
ELSEVIER
DOI: 10.1016/j.ejpb.2019.09.022
关键词
Water-soluble peptide; Hydrophobic ion-pairing complex; Encapsulation efficiency; Initial burst release; Self-healing
资金
- National Natural Science Foundation of China [21476111, 21776136, 81803439]
- Program for Innovative Research Team in Universities of Jiangsu Province
- Jiangsu Synergetic Innovation Center for Advanced BioManufacture [XTD1820]
- Natural Science Foundation of the Higher Education Institutions of Jiangsu Province [18KJB350003]
- Youth Foundation of Jiangsu province [BK20180699]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX18_1104, KYCX18_1115]
Poor encapsulation and high initial burst were two major obstacles for the water-soluble peptide drug loaded microspheres preparation using the industrial emulsification method. In the present study, we hypothesized that the hydrophobic ion-pairing (HIP) complex strategy with a further healing of the pores within the microspheres may improve drug encapsulation and initial burst release. DSS was chosen as the most suitable one among the three test ion-pairing agents (SDS, DSS and STC) due to its high binding efficiency with drug and reversible dissociation capacity in presence of counter ions. The formation of HIP complex between octreotide acetate and DSS successfully reversed the highly water-soluble nature of the drug. A specific S/O/W method was adopted to encapsulate such drug containing HIP complex. The encapsulation efficiency of the drug was greatly improved compared with the conventional W1/O/W2 method (from 44% to 90%). Under the optimal healing conditions (the healing time 6 h, temperature 40 degrees C and 4% DEP content), the pores within the microspheres were effectively healed. Initial burst amount of octreotide acetate in S/O/W microspheres decreased to 3.56%. The pore healing effect was further confirmed by the scanning electron microscopy and fluorescence microscopy results. In the process of testing the drug release performance of such new strategy in vitro and in vivo, a more satisfactory single phase release profile with sustained and steady drug release was observed. These results suggested that the modified HIP strategy could be a promising platform for water-soluble peptide encapsulation with high encapsulation efficiency, low initial burst and stable drug release mechanism.
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