Development and characterization of new insulin containing polysaccharide nanoparticles

被引:192
作者
Sarmento, Bruno
Ribeiro, Antonio
Veiga, Francisco
Ferreira, Domingos
机构
[1] Univ Porto, Fac Pharm, Dept Pharmaceut Technol, P-4050030 Oporto, Portugal
[2] ISCSN, Dept Pharmaceut Technol, Gandra, Portugal
[3] Univ Coimbra, Fac Pharm, Dept Pharmaceut Technol, Coimbra, Portugal
关键词
chitosan; dextran sulfate; insulin; nanoparticles; pH-dependent release; bioactivity;
D O I
10.1016/j.colsurfb.2006.09.012
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
A nanoparticle insulin delivery system was prepared by complexation of dextran sulfate and chitosan in aqueous solution. Parameters of the formulation such as the final mass of polysaccharides, the mass ratio of the two polysaccharides, pH of polysaccharides solution, and insulin theorical loading were identified as the modulating factors of nanoparticle physical properties. Particles with a mean diameter of 500 nm and a zeta potential of approximately -15 mV were produced under optimal conditions of DS:chitosan mass ratio of 1.5:1 at pH 4.8. Nanoparticles showed spherical shape, uniform size and good shelf-life stability. Polysaccharides complexation was confirmed by differential scanning calorimetry and Fourier transformed infra-red spectroscopy. An association efficiency of 85% was obtained. Insulin release at pH below 5.2 was almost prevented up to 24 h and at pH 6.8 the release was characterized by a controlled profile. This suggests that release of insulin is ruled by a dissociation mechanism and DS/chitosan nanoparticles are pH-sensitive delivery systems. Furthermore, the released insulin entirely maintained its immunogenic bioactivity evaluated by ELISA, confirming that this new formulation shows promising properties towards the development of an oral delivery system for insulin. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:193 / 202
页数:10
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