4.8 Article

Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 121, Issue 3, Pages 156-167

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2007.05.026

Keywords

brain delivery; wheat germ agglutinin; vasoactive intestinal peptide; nanoparticles; intranasal administration

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The development of biotech drugs such as peptides and proteins that act in the central nervous system has been significantly impeded by the difficulty of delivering them across the blood-brain barrier. The surface engineering of nanoparticles with lectins opened a novel pathway to the absorption of drugs loaded by biodegradable poly (ethylene glycol)-poly (lactic acid) nanoparticles in the brain following intranasal administration. In the present study, vasoactive intestinal peptide, a neuroprotective peptide, was efficiently incorporated into the poly (ethylene glycol)-poly (lactic acid) nanoparticles modified with wheat germ agglutinin and the biodistribution, brain uptake and neuroprotective effect of the formulation were assessed. The area under the concentration-time curve of intact 125 I-vasoactive intestinal peptide in brain of mice following the intranasal administration of 125 I-vasoactive intestinal peptide carried by nanoparticles and wheat germ agglutinin-conjugated ones was significantly enlarged by 3.5 similar to 4.7 folds and 5.6 similar to 7.7 folds, respectively, compared with that after intranasal application of 125 I-vasoactive intestinal peptide solution. The same improvements in spatial memory in ethylcholine aziridium-treated rats were observed following intranasal administration of 25 mu g/kg and 12.5 mu g/kg of vasoactive intestinal peptide loaded by unmodified nanoparticles and wheat germ agglutinin-modified nanoparticles, respectively. Distribution profiles of wheat germ agglutinin-conjugated nanoparticles in the nasal cavity presented their higher affinity to the olfactory mucosa than to the respiratory one. Inhibition experiment with specific sugars suggested that the interaction between the nasal mucosa and the wheat germ agglutinin-functionalized nanoparticles were due to the immobilization of carbohydrate-binding pockets on the surface of the nanoparticles. The results clearly indicated wheat germ agglutinin-modified nanoparticles might serve as promising carriers especially for biotech drugs such as peptides and proteins. (C) 2007 Elsevier B.V All rights reserved.

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