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

To develop a new polypeptide delivery system, insulin nano-aggregates with sizes of 100–230 nm 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(α,...

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Bibliographic Details
Published in:International journal of pharmaceutics 2006-11, Vol.324 (2), p.158-167
Main Authors: Fan, Y.F., Wang, Y.N., Fan, Y.G., Ma, J.B.
Format: Article
Language:English
Subjects:
Adsorption
Biological and medical sciences
Chemical Precipitation
Chitosan - administration & dosage
Drug Stability
General pharmacology
Hydrogen-Ion Concentration
Insulin
Insulin - administration & dosage
Insulin - chemistry
Layer-by-layer adsorption
Malates - administration & dosage
Medical sciences
Microscopy, Electron, Scanning
Nanoparticles
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Poly(α,β- l-malic acid)
Polymers - administration & dosage
Sodium Chloride - administration & dosage
Solubility
Water-soluble chitosan
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Summary:To develop a new polypeptide delivery system, insulin nano-aggregates with sizes of 100–230 nm 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(α,β- 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 100–250 nm 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2006.05.062