Needle-Free Dermal Delivery of a Diphtheria Toxin CRM197Mutant on Potassium-Doped Hydroxyapatite Microparticles
Weissmueller NT., Schiffter HA., Carlisle RC., Rollier CS., Pollard AJ.
ABSTRACTInjections with a hypodermic needle and syringe (HNS) are the current standard of care globally, but the use of needles is not without limitation. While a plethora of needle-free injection devices exist, vaccine reformulation is costly and presents a barrier to their widespread clinical application. To provide a simple, needle-free, and broad-spectrum protein antigen delivery platform, we developed novel potassium-doped hydroxyapatite (K-Hap) microparticles with improved protein loading capabilities that can provide sustained local antigen presentation and release. K-Hap showed increased protein adsorption over regular hydroxyapatite (P< 0.001), good structural retention of the model antigen (CRM197) with 1% decrease in α-helix content and no change in β-sheet content upon adsorption, and sustained releasein vitro. Needle-free intradermal powder inoculation with K-Hap–CRM197induced significantly higher IgG1 geometric mean titers (GMTs) than IgG2a GMTs in a BALB/c mouse model (P< 0.001) and induced IgG titer levels that were not different from the current clinical standard (P> 0.05), namely, alum-adsorbed CRM197by intramuscular (i.m.) delivery. The presented results suggest that K-Hap microparticles may be used as a novel needle-free delivery vehicle for some protein antigens.