Effective humoral immune response from a H1N1 DNA vaccine delivered to the skin by microneedles coated with PLGA-based cationic nanoparticles

Abstract

Intradermal DNA vaccination is a promising method of immunization that overcomes some practical drawbacks of conventional intramuscular vaccinations. However, it is difficult to deliver DNA vaccines to target cells in the skin and polyplexes. This study outlines the development of an intradermal pH1N1 DNA vaccine delivery platform using microneedles (MNs) coated with a polyplex containing poly lactic-co-glycolic acid/polyethyleneimine (PLGA/PEI) nanoparticles (NPs). Stainless steel MNs with enhanced hydrophilicity have been manufactured by silanization, which improves coating efficiency. MNs coated with the polyplex encapsulating pDNA vaccine were prepared by optimizing the N/P ratio, with a 6:1 ratio showing the highest transfection efficiency in mammalian cells. Polyplexes were coated on MNs without severe aggregation of the polyplex in the dry form. The coated polyplex rapidly dissolved in porcine skin (within 5min) and induced a greater humoral immune response than that of intramuscular polyplex delivery or naked pH1N1 DNA vaccine delivery by a dry-coated MN. These results indicate that intradermal delivery of pDNA vaccines within a cationic polyplex coated on MNs has potential in skin immunizations.

Keywords: Microneedle; PLGA; Polyethyleneimine (PEI); Skin vaccination; pH1N1 DNA vaccine.