Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 327, Issue 1-2, Pages 153-159Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2006.07.026
Keywords
wheat germ agglutinin; insulin; solid lipid nanoparticles; oral administration
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The aim of this study was to design and characterize lectin-modified solid lipid nanoparticles (SLNs) containing insulin and to evaluate the potential of the lectin-modified colloidal carriers for oral administration of peptide and protein drugs. SLNs were prepared by three different methods. For comparison, some insulin-loaded SLNs were modified with wheat germ agglutinin-N-glutaryi-phosphatidylethanolamine (WGA-N-glut-PE). The particle size, zeta potential and entrapment efficiency of insulin-loaded SLNs were determined. Insulin-loaded SLNs prepared by an appropriate modification of the double dispersion method yielded the highest drug entrapment efficiency, which was more than 60%. In vivo experiments were carried out using insulin-loaded SLNs and WGA-modified SLNs prepared by this method. SLNs and WGA-modified SLNs protected insulin against degradation by digestive enzymes in vitro. The stabilizing effect of WGA-modified SLNs was greater than that observed in SLNs. After oral administration of insulin-loaded SLNs or WGA-modified SLNs to rats, the relative pharmacological bioavailabilities were 4.46% and 6.08%, and the relative bioavailabilities were 4.99% and 7.11 %, respectively, in comparison to subcutaneous injection of insulin. These results demonstrated that SLNs and WGA-modified SLNs promoted the oral absorption of insulin. (c) 2006 Elsevier B.V. All rights reserved.
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