Polyphosphazene Microneedles for Intradermal Vaccination

Skin is an attractive organ for administration of vaccines since it constitutes an anatomic barrier, defending the body against external pathogens. Since the skin is home to a larger population of dendritic cells than muscle tissue, intradermal vaccines typically induce stronger immune responses than intramuscular vaccines and provide the basis for a significant vaccine sparing effect. Microneedle technology, which utilizes patches with sub-millimeter structures to pierce the stratum corneum and deliver vaccines in the epidermis, is an especially attractive pathway for intradermal delivery. Microneedles are designed to combine vaccine formulation, often as a solid coating, and metal, as a supporting material to provide the required mechanical strength. Once applied to the skin, these formulations dissolve or degrade to release vaccine antigen in the skin compartment. Solid vaccine formulations are especially attractive since they also offer improved shelf life and reduced dependence on temperature-controlled supply chains. These microneedles can also be self-administered and safely disposed of.  All these properties are highly desirable during times of vaccines shortages, such as epidemic emergencies, and result in major global health benefits, particularly in areas where access to healthcare personnel is an issue.

Although the microneedle immunization approach appears to be promising, its technical realization faces significant challenges, such as incompatibility of the currently employed vaccine adjuvants with intradermal delivery technologies. IBBR is engaged in the development of microneedle technology advancing a unique approach – applying polyphosphazene macromolecules both as microfabrication material and vaccine adjuvants.  It has been already proven that the dual function molecules allow for adjuvant compatible intradermal delivery and improved microneedle fabrication processes. Remarkably, in vivo studies demonstrated a strong synergy between polyphosphazene adjuvants and intradermal administration. These findings clearly indicate that the potency of polyphosphazene microneedles is superior to what was expected on the basis of their intramuscular immunoadjuvant activity and the results for non-adjuvanted microneedles. The research is now focused on further advancement of this technology focusing on vaccines against diseases with a greatest threat of epidemic emergencies, such as Ebola, Anthrax and others.