Determining the Feasibility of a Liposomal Prototype Formulation for GC-C Agonist Peptide Drug Delivery

Abstract

The purpose of this study was to determine the feasibility of using a liposomal formulation for the systemic delivery of a GC-C agonist peptide drug. Peptide drugs have increased in numbers lately but are limited by delivery challenges. Liposomes can overcome some of those challenges. Peptides themselves are sensitive to processing conditions but GC-C agonists are stabilized by multiple disulfide bonds. Processing conditions, lipid types and drug solutions for preparing liposomes were evaluated. The drug load efficiency and peptide degradation were measured by quantitation of the drug and impurities by HPLC. The formation of multimers was monitored by size exclusion chromatography. Two prototype batches were stored at two temperatures to determine the stability of the liposomal formulation. The peptide degradation, multimer formation, and leakage rate was evaluated. The results discussed here show the feasibility of liposomes containing linaclotide to be developed as a formulation that may be functionalized with PEG or a mucoadhesive polymer that has potential to be used in an inhaler, nasal pump, or other new delivery system that can utilize a liposomal solution to deliver the drug to systematic targets, although further optimization is needed before a scaled-up, commercial formulation is realized.