Synthetic peptides derived from naturally occurring host defence peptides, HDPs, have garnered significant attention as novel pharmaceuticals, particularly as alternatives to antibiotics and for immunomodulatory applications. One of the barriers to advancing synthetic peptides for therapeutic applications is their tendency to aggregate under specific ionic conditions similar to those they would encounter in vivo. Formulating peptides with biocompatible excipients that prevent solventâ€induced peptide aggregation represents a possible solution to this aggregation issue; however, this strategy has not been systematically explored.
In work presented in Peptide Science, researchers in the Hancock Lab, describe the screening of various polymeric substances, including hyaluronic acid, carboxymethyl cellulose and hydroxypropyl methyl cellulose, as formulation candidates for HDPs and identified derivatized hyperbranched polyglycerols, dHPGs, as a biocompatible excipient that limits peptide aggregation. Notably, the immunomodulatory activity of a synthetic innate defence regulator peptide, IDRâ€1018, formulated with dHPG was retained when evaluated against both peripheral blood mononuclear cells and human bronchiolar epithelial cells in vitro.
Further characterization of dHPG polymers revealed that decreasing the negative charge density on the polymer surface potentiated the cytotoxic effects of IDRâ€1018, emphasizing the need to optimize this parameter for future peptide delivery formulations. Importantly, the dHPG formulated IDRâ€1018 inhibited peptide aggregation in vitro in the presence of mucin as well as in vivo when injected subcutaneously into CD1 mice. This study highlights the potential use of dHPGs as formulation candidates for synthetic HDPs and identifies important considerations regarding their physicoâ€chemical properties and relevance to immunomodulatory applications.
Identification of an IDR Peptide Formulation Candidate that Prevents Peptide Aggregation and Retains Immunomodulatory Activity
Evan F. Haney Kelli C. Wuerth Negin Rahanjam Nazila Safaei Nikouei Arvin Ghassemi Mahsa Alizadeh Noghani Anthony Boey Robert E. W. Hancock
Peptide Science, Volume 110, Issue 3, Special Issue: Emerging Peptide Science in Australia, May 2018