Effects of Hydrophilic Cyclodextrins on Aggregation of Recombinant Human Growth Hormone

Abstract

The different inhibitory effect of CyDs is dependent not only on the structure and property of CyD itself but also the nature of the denaturing stimulus. The current results suggested that hydrophilic beta-CyDs can effectively inhibit the aggregation of rhGH. Thus, hydrophilic beta-CyDs may be potentially useful excipients for parenteral preparation of rhGH.

Stability of Protein Pharmaceuticals: An Update

“…Addition of β-CDs has been reported to increase the physical stability of hGH with respect to aggregation (419,420). In both cases, the CD was shown to bind to the native state of the protein with a millimolar binding constant.…”

The Effect of Cyclodextrins on Chemical and Physical Stability of Glucagon and Characterization of Glucagon/γ-CD Inclusion Complexes

“…24 In agreement, there are studies describing the poor effect of g-CD on solubility or stability properties of peptides/proteins. For example, Otzen et al 18 showed that g-CD was much less effective than b-CD in solubilizing human growth hormone.…”

“…Thus, the ability of CDs to improve the physical stability of glucagon is a consequence of inclusion complex formation, which has also been described with other peptides. 18,24,25,31 In addition, the higher viscosity of the solutions containing CDs may also have affected the physical stability of glucagon by delaying the aggregation in the present study.…”

“…31 By preventing such hydrophobic interactions, CDs are able to inhibit the initiation of aggregation. Thus, the aggregation of human growth hormone 18,24 and insulin 25,31 has been decreased using CDs. Based on the study of the aggregation behavior of glucagon and secretin, a peptide with high sequential structural homology with glucagon, it was suggested that Trp25, Tyr10, Tyr13, and Phe22 are crucial in the initiation of aggregation of glucagon.…”

Effect of 2‐hydroxypropyl‐β‐cyclodextrin on thermal stability and aggregation of glycogen phosphorylase b from rabbit skeletal muscle

“…Many reports have indicated that protein stability against thermal and chemical denaturation and aggregation may be increased in the presence of cyclodextrins, which probably form complexes with accessible hydrophobic side chain of aminoacids. 1 Formation of these complexes with proteins enhances their solubility in aqueous medium and diminishes protein aggregation inducing a decrease in the aggregate size. 2,3 Cyclodextrins can be useful stabilizing excipients in the preparation of spraydried protein pharmaceuticals.…”