Investigation of sterile hydrogels as topical vehicles for APOSECTM, a stressed peripheral blood mononuclear cell secretome for the treatment of poorly healing wounds.

APOSECTM, a complex mixture of secreted proteins, lipids, and exosomes from stressed peripheral blood monocytes, is currently in clinical trials for the treatment of chronic wounds. When applied to open wounds, 1 mL reconstituted APOSECTM lyophilisate is syringe-mixed with 3 g sterile hydrogel prior to administration. This study investigates the pharmaceutical performance of this novel administration system. A gel formulation (APOgel) was developed for terminal sterilisation in pre-filled syringes with post-sterilisation viscosity (∼325-350  Pa·s at 1  s-1) comparable to a commercial benchmark gel. Syringe mixing of APOgel with a liquid APOSECTM surrogate (3:1) reduced viscosity by ∼ 67% but was highly reproducible across different operators (CV < 6%). Administration of three sequential dose units of the mixture from the syringe revealed an ∼ 20% higher content of active ingredients in the first and final dispensed compared to the middle unit, indicating non-uniform mixing in the closed syringe system. In vitro release studies over 72  h showed a 32% and 48% higher release of a small molecule marker and total proteins from the sterile APOgel compared to the benchmark, while total release at 72 h was 100% for small molecules and 25% for total proteins from the APOgel system. Efficacy studies in a murine wound healing model showed no significant difference between APOgel and the benchmark. Overall, APOgel shows potential as a hydrogel platform for topical administration but its mixing system, release kinetics, and test methods could benefit from further optimisation before broader use.