US EPA

4118876 

Journal Article 

Development of a freeze-dried formulation of insulin-loaded chitosan nanoparticles intended for nasal administration 

Fernandez-Urrusuno, R; Romani, D; Calvo, P; Vila-Jato, JL; Alonso, MJ 

1999 

1 

STP Pharma Sciences
ISSN: 1157-1489 

9 

5 

429-436 

WOS:000084172000007 

The aim of this work was to develop a freeze-dried formulation of insulin-loaded chitosan nanoparticles and to assess their efficacy for reducing the plasma glucose levels following nasal administration. Chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions and then characterized in vitro (size, zeta potential, insulin lending and release) and in vivo (plasma glucose levels). The nanoparticles were also freeze-dried in the presence of various cryoprotective agents and then characterized upon reconstitution in water. Fresh chitosan nanoparticles displayed a positive charge and a high insulin loading (up to 55%, w/w). In vitro release studies showed that insulin was totally released from the nanoparticles in less than I h, Upon freeze-drying in the presence of trehalose or sucrose, the nanoparticles were freely reconstituted in water without a significant change in their size, zeta potential, insulin loading and release rate. The in vivo evaluation in conscious rabbits revealed that insulin-associated nanoparticles are able to reduce the plasma glucose levels to a greater extent than insulin chitosan solutions. Furthermore, the in vivo efficacy of the reconstituted insulin-loaded nanoparticles administered intranasally was Sully maintained. Consequently;, freeze-dried chitosan nanoparticles can be proposed as useful vehicles for increasing the nasal absorption of insulin. 

chitosan nanoparticles; freeze-drying; nasal administration; insulin