TY - JOUR

T1 - Preparation and characterization of insulin-surfactant complexes for loading into lipid-based drug delivery systems

AU - Li, Ping

AU - Nielsen, Hanne Mørck

AU - Fano, Mathias

AU - Müllertz, Anette

N1 - Copyright © 2013 Wiley Periodicals, Inc.

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - Dimethyl Sulfoxide

KW - Drug Carriers

KW - Freeze Drying

KW - Hypoglycemic Agents

KW - Insulin

KW - Lipids

KW - Protein Structure, Secondary

KW - Spectroscopy, Fourier Transform Infrared

KW - Surface-Active Agents

U2 - 10.1002/jps.23640

DO - 10.1002/jps.23640

M3 - Journal article

C2 - 23839923

VL - 102

SP - 2689

EP - 2698

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 8

ER -