Ajay Taluja1, You Han Bae. 1. Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA.
Abstract
PURPOSE: This study is to investigate whether poly(ethylene glycol) (PEG)-b-poly(L-histidine) [PEG-polyHis] can reduce aggregation of insulin in aqueous solutions on agitation by forming ionic complexes. MATERIALS AND METHODS: Insulin aggregation on agitation was monitored spectrophotometrically and by fibrillation studies with a dye Thioflavin T. Pluronic F-127 as a control and PEG-polyHis as a novel multifunctional excipient were added to prevent destabilization of insulin. Conformation of insulin was evaluated in a circular dichroism (CD) study. RESULTS: Ionic interactions between insulin and PEG-polyHis were induced in the pH range: 5.5-6.5. pH 5.5 was selected for further evaluation based on particle size/zeta potential studies. Ionic complexation with PEG-polyHis is more effective at pH 5.5 in stabilizing insulin (75% of insulin retained versus 0% with no excipient) than Pluronic F-127 (42% retained). PEG-polyHis guards against insulin aggregation in non-complexing pH conditions (pH 7.4), 64% insulin retained versus 58% with F-127 and 0% with no excipient) pointing to the potential role played by PEG in modulation of insulin surface adsorption. Rate of fibrillation was higher for plain insulin compared with addition of PEG-polyHis and Pluronic F-127 at both pH. CONCLUSIONS: Understanding and manipulation of such polyelectrolyte-protein complexation will likely play a role in protein stabilization.
PURPOSE: This study is to investigate whether poly(ethylene glycol) (PEG)-b-poly(L-histidine) [PEG-polyHis] can reduce aggregation of insulin in aqueous solutions on agitation by forming ionic complexes. MATERIALS AND METHODS:Insulin aggregation on agitation was monitored spectrophotometrically and by fibrillation studies with a dye Thioflavin T. Pluronic F-127 as a control and PEG-polyHis as a novel multifunctional excipient were added to prevent destabilization of insulin. Conformation of insulin was evaluated in a circular dichroism (CD) study. RESULTS: Ionic interactions between insulin and PEG-polyHis were induced in the pH range: 5.5-6.5. pH 5.5 was selected for further evaluation based on particle size/zeta potential studies. Ionic complexation with PEG-polyHis is more effective at pH 5.5 in stabilizing insulin (75% of insulin retained versus 0% with no excipient) than Pluronic F-127 (42% retained). PEG-polyHis guards against insulin aggregation in non-complexing pH conditions (pH 7.4), 64% insulin retained versus 58% with F-127 and 0% with no excipient) pointing to the potential role played by PEG in modulation of insulin surface adsorption. Rate of fibrillation was higher for plain insulin compared with addition of PEG-polyHis and Pluronic F-127 at both pH. CONCLUSIONS: Understanding and manipulation of such polyelectrolyte-protein complexation will likely play a role in protein stabilization.
Authors: Jason Li; Michael K Chu; Brian Lu; Sako Mirzaie; Kuan Chen; Claudia R Gordijo; Oliver Plettenburg; Adria Giacca; Xiao Yu Wu Journal: Drug Deliv Transl Res Date: 2017-08 Impact factor: 4.617