Abstract
Insulin suffers from poor oral bioavailability, but lipid-based drug delivery systems (DDS) may constitute promising tools for improving this. Loading of protein drugs into lipid matrices may, however, be challenging, and different formulation approaches must be taken to achieve sufficient loading and preservation of native structure. The aim of the present study was to characterize insulin after complexation with biocompatible surfactants to improve loading into lipid-based DDS. Insulin-surfactant complexes were prepared by freeze-drying with distearyldimethylammonium bromide or soybean phospholipid as complexing surfactant and dimethyl sulfoxide (DMSO) as solvent. Significant change in secondary structure of insulin freeze dried from DMSO was observed using Fourier transform infrared spectroscopy. Changes were quantitatively smaller in the presence of surfactants, demonstrating both a stabilizing effect of surfactants, but also a nonnative secondary structure in the solid state. Finally, circular dichroism analysis of rehydrated complexes showed that the processing did not irreversibly alter the secondary structure of insulin. In short, the present study demonstrates changes in the secondary structure of insulin after freeze-drying from DMSO, constituting a potential generic issue with this technique for protein processing. In the specific case of insulin, the changes were found to be reversible, explaining the success of this strategy in previous studies.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Pharmaceutical Sciences |
| Vol/bind | 102 |
| Udgave nummer | 8 |
| Sider (fra-til) | 2689-98 |
| Antal sider | 10 |
| ISSN | 0022-3549 |
| DOI | |
| Status | Udgivet - aug. 2013 |