Compositions and methods for improving systemic delivery, tolerability, and efficacy of cationic macrocyclic peptides (COMPOSITIONS AND METHODS FOR ENHANCING SYSTEMIC DELIVERABILITY, TOLERABILITY, AND EFFICACY OF CATIONIC MACROCYCLIC PEPTIDES)

摘要

Compositions are provided for the formulation of θ-defensin and/or θ-defensin analogues which are well suited for parenteral administration. Such formulations provide [theta]-defensin and/or [theta]-defensin analogs in a weakly acidic buffer comprising propylene glycol. Surprisingly, the inventors have found that such formulations increase the bioavailability of θ-defensin and/or θ-defensin analogs so provided at least 10 times compared to conventional isotonic saline solutions, and such formulations are bioavailable in human subjects compared to animal models. We found that it significantly improved the utilization rate. The inventors have also found that such formulations advantageously exhibit a low viscosity at high peptide concentration, which reduces the injection volume and allows sterilization by simple filtration.