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Int J Pharm. 2006 Nov 6;324(2):158-67. Epub 2006 Jun 3.

Preparation of insulin nanoparticles and their encapsulation with biodegradable polyelectrolytes via the layer-by-layer adsorption.

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1
Key Laboratory of Functional Polymer Materials (Ministry of Education), Institute of Polymer Chemistry, Nankai University, Tianjin 300071, PR China.

Abstract

To develop a new polypeptide delivery system, insulin nano-aggregates with sizes of 100-230nm were prepared by the salting out method with NaCl and encapsulated via the layer-by-layer (LbL) adsorption to provide the insulin nanoparticles shelled with two oppositely charged polyelectrolytes. Poly(alpha,beta-l-malic acid) (PMA) and water-soluble chitosan (WSC) as the weak polyelectrolytes with good biodegradability and biocompatibility in vivo were chosen to be the encapsulating materials of the LbL adsorption. In the preparation of the insulin nano-aggregates, the NaCl concentration and pH in the medium obviously affected yield and particle size of the insulin nano-aggregates. After eight adsorption cycles of the polyelectrolytes on the insulin nano-aggregates, the insulin-polyelectrolyte nanoparticles with the sizes of 100-250nm were obtained with about 20% insulin loss. The insulin release from the nanoparticles was mostly pH-dependent owing to sensitivity of the weak polyelectrolytes to pH. Insulin was hardly released from the nanoparticles in a medium at pH 4-5 while it could be released at pH 7.4, corresponding to the pH of the human blood and the body fluid. A burst effect was also observed although it could be reduced via increasing the polyelectrolyte layers of PMA and WSC assembled on insulin nano-aggregates.

PMID:
16814967
DOI:
10.1016/j.ijpharm.2006.05.062
[Indexed for MEDLINE]

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