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Aminated Gelatin Microspheres As A Nasal Delivery System For Peptide Drugs: Evaluation Of In Vitro Release And In Vivo Insulin Absorption In Rats.

J. Wang, Y. Tabata, K. Morimoto
Published 2006 · Chemistry, Medicine

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Aminated gelatin microspheres (AGMS) was investigated as a nasal drug delivery system for peptide drugs. The in vitro drug release from microspheres was evaluated using a fluorescein-labeled insulin (RITC-insulin) and FITC-dextran with a molecular weight of 4.4 kDa (FD-4) as model drugs. RITC-insulin release from AGMS was significantly slower than from native gelatin microspheres (GMS), with a cumulate release of 18.4% and 32.4% within 30 min, and 56.9% and 75.1% within 8 h respectively. However, the release of FD-4 from both AGMS and GMS was quite rapid and no difference was observed for the two microspheres. The electrostatic interactions between the model drugs and the microspheres were supposed to be the main factor that controlled the release behavior. The absorption enhancing effect was estimated by measuring the changes of plasma glucose concentrations of healthy rats following intranasal administration of insulin-incorporated microspheres in both suspension and dry powder forms. AGMS could significantly increase the nasal absorption of insulin in rats when administered in a dry powder formulation, but no significant hypoglycemic effect was observed when given in suspensions. One of the mechanisms for the increased insulin absorption was attributed to the hydrogel nature of the microspheres that could absorb water from the nasal mucosa and thus resulted in a temporarily dehydration of the epithelium membrane and opening of the tight junctions. The positive charge of the AGMS has also evidently contributed to the absorption enhancing effect. In addition, the mucoadhesive properties of AGMS might also have played a role to the total effect. AGMS might be a new candidate carrier for the nasal delivery of peptide drugs.
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