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The captopril/Chitosan-gelatin net-polymer microspheres (CTP/CGNPMs) were prepared using Chitosan (CTS) and gelatin (GT) by the methods of emulsification, cross-linked reagent alone or in combination and microcrystalline cellulose (MCC) added in the process of preparation of microspheres, which aimed to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril (CTP). The results indicated that CTP/CGNPMs had a spherical shape, smooth surface and integral structure inside but no adhesive phenomena in the preparation. The size distribution ranged from 220 μm to 280 μm. The CTP release test in vitro demonstrated that CTP/CGNPMs played the role of retarding the release of CTP compared with ordinary CTP tablets. The release behaviors of CGNPMS were influenced by preparation conditions such as experimental material ratio (EMR) and composition of cross linking reagents. Among these factors, the EMR (1/4), CLR (FA+SPP) and 0.75% microcrystalline cellulose (MCC) added to the microspheres constituted the optimal scheme for the preparation of CTP/CGNPMs. The ER, DL and SR of CTP/CGNPMs prepared according to the optimal scheme were 46.23±4.51%, 9.95±0.77% and 261±42%, respectively. The CTP/CGNPMs had the good characteristics of sustained release of drug and the process of emulsification and cross-linking were simple and stable. The CGNPMs are likely to be an ideal sustained release formulation for water-soluble drugs.