Needle-Free Dermal Delivery of a Diphtheria Toxin CRM197Mutant on Potassium-Doped Hydroxyapatite Microparticles

<jats:title>ABSTRACT</jats:title><jats:p>Injections 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 (<jats:italic>P</jats:italic>&lt; 0.001), good structural retention of the model antigen (CRM<jats:sub>197</jats:sub>) with 1% decrease in α-helix content and no change in β-sheet content upon adsorption, and sustained release<jats:italic>in vitro</jats:italic>. Needle-free intradermal powder inoculation with K-Hap–CRM<jats:sub>197</jats:sub>induced significantly higher IgG1 geometric mean titers (GMTs) than IgG2a GMTs in a BALB/c mouse model (<jats:italic>P</jats:italic>&lt; 0.001) and induced IgG titer levels that were not different from the current clinical standard (<jats:italic>P</jats:italic>&gt; 0.05), namely, alum-adsorbed CRM<jats:sub>197</jats:sub>by 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.</jats:p>