Intradermal immunization using microfabricated needles represents a potentially powerful technology, which can enhance immune responses and provide antigen sparing. Solid vaccine formulations, which can be coated onto microneedle patches suitable for simple administration, can also potentially offer improved shelf-life. However the approach is not fully compatible with many vaccine adjuvants including alum, the most common adjuvant used in the vaccine market globally. Here, we introduce a polyphosphazene immunoadjuvant as a biologically potent and synergistic constituent of microneedle-based intradermal immunization technology. Poly[di-(carboxylatophenoxy)phosphazene], PCPP, functions both as a vaccine adjuvant and as a key microfabrication material. When used as part of an intradermal delivery system for hepatitis B surface antigen, PCPP demonstrates superior activity in pigs compared to intramascular administration and significant antigen sparing potential. It also accelerates the microneedle fabrication process and reduces its dependence on the use of surfactants. In this way, PCPP-coated microneedles may enable effective intradermal vaccination from an adjuvanted patch delivery system. polyphosphazenes ͉ vaccine adjuvants

Degradation of a water-soluble polyphosphazene, poly[di(carboxylatophenoxy)phosphazene], disodium salt (PCPP) has been studied in aqueous solutions at elevated temperature. This synthetic polyelectrolyte is of interest as vaccine adjuvant and its degradability constitutes an important component of its safety and formulation stability profiles. The degradation process is manifested by a gradual reduction in the molecular weight of the polymer and cleavage of side groups, which is consistent with previously reported data on hydrolytical breakdown of water-soluble polyphosphazenes. The kinetics of hydrolytical degradation exhibits distinct pH dependence and the process is faster in solutions with lower pH. Remarkably, a number of hydrogen bond forming additives, such as polyethylene glycol and Tween displayed a dramatic accelerating effect on the degradation of PCPP, whereas inorganic salts, such as sodium chloride and potassium chloride, showed a trend for its retardation. The results can be potentially explained on the basis of acid promoted hydrolysis mechanism and macromolecular interactions in the system.

Applications of polyelectrolytes as pharmaceutical excipients or biologically active agents generated an increased interest in formulations, in which ionic macromolecules share the same milieu with protein drugs or vaccine antigens. Macromolecular interactions, which often take place in such systems, can potentially impact formulation activity and stability. The present article reports that poly[di(carboxylatophenoxy)phosphazene], disodium salt (PCPP), which has been previously shown to be a potent vaccine adjuvant, also displays a strong protein stabilizing effect in aqueous solutions that can be significantly amplified in the presence of nonionic surfactants. The phenomenon is studied in the context of macromolecular interactions in the system and is linked to the formation of PCPP-protein and PCPP-protein-surfactant complexes.

Microneedles containing PCPP coatings provide improved protein stability, modulated release, and protein-friendly microfabrication process.

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