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�й�ҩѧ��־ 2014, Vol. 49 Issue (16) :1414-1419    DOI: 10.11669/cpj.2014.16.012
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SUN Chuan, XING Yang, HU Hua-ying, LIANG Yun-xing, FAN Bo, LIANG Gui-xian*
Department of Pharmaceutics, School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, China

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Abstract�� OBJECTIVE To develop pH-sensitive thiolated chitosan nanoparticles and evaluate the mucosal permeation effect of the nanoparticles for low molecular weight heparin. METHODS The pH-sensitive thiolated chitosan nanoparticles were prepared by ionic cross-linking reaction and characterized for the shape, particle size, Zeta potential, drug entrapment efficiency and loading capacity. In vitro release of low molecular weight heparin from the prepared nanoparticles was evaluated in 0.1 mol�L-1 HCl solution and phosphate buffered saline (PBS) at pH 6.8 using the dialysis method. The intestinal permeability was estimated utilizing Franz diffusion cell system. RESULTS The obtained nanoparticles were found to be approximately spherical with the mean particles size of (329.6?7.3) nm and a positive Zeta potential of (34.5?2.25) mV; the entrapment efficiency and loading capacity of the NPs were (97.75?0.02)% and (12.463?0.003) u�mg-1, respectively. In 0.1 mol�L-1 HCl solution (pH 1.0) the release rate of low molecular weight heparin within 24 h from thiolated chitosan nanoparticles was faster than that from pH-sensitive thiolated chitosan nanoparticles with a significant difference (P<0.05).Whereas, in the case of release in PBS (pH 6.8), no noticeable difference was observed in the drug release behavior between pH-sensitive and non-pH-sensitive nanoparticles. The cumulative amount of permeability on carp intestine mucosa in vitro within 8 h were (7.23?0.21), (6.99?0.79), (5.62?0.22) and (3.88?0.76) u�cm-2 for pH-sensitive thiolated chitosan nanoparticles, thiolated chitosan nanoparticles, chitosan nanoparticles and low molecular weight heparin solution, respectively. CONCLUSION The pH-sensitive thiolated chitosan nanoparticles have a significant penetration enhancing effect for low molecule weight heparin.
Keywords�� low molecular weight heparin,   pH-sensitive,   thiolated chitosan,   nanoparticle,   mucosal penetration     
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SUN Chuan, XING Yang, HU Hua-Ying etc .Preparation and In vitro Mucosal Penetration Evaluation of pH-Sensitive Thiolated Chitosan Nanoparticles for Low Molecular Weight Heparin Delivery[J]  Chinese Pharmaceutical Journal, 2014,V49(16): 1414-1419
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