Oral DNA delivery using spiky silica nanoparticles: a pharmacokinetic understanding

Nucleic acid (NA)-mediated vaccination has gained huge interest in recent years. In particular, DNA vaccines can provide long lasting immunity at a relatively low cost. Subcutaneous and intradermal injections are the common routes of administration for DNA vaccines, yet there are no oral DNA vaccines available on the market. Despite the well-known DNA degradation problem and delivery barriers in the gastrointestinal tract (GIT), the pharmacokinetics of orally delivered DNA are rarely reported, which is crucial for determining an appropriate timeline for vaccination and the ultimate immune response. In this study, an oral DNA delivery system based on spiky silica nanoparticles (SNPs) has been designed; then, the pharmacokinetics of this oral DNA nanovaccine formulation and the immune responses have been investigated. By loading DNA in PEGylated spiky silica nanoparticles (PEG-SNPs) and then encapsulating into pH-responsive enteric-coated capsules, DNA can be protected from harsh gastric pH and delivered successfully in the intestinal region. It is demonstrated that a time interval of 3 days for vaccination is optimal for antigen protein expression and antigen-specific antibody response. This study offers insights into the strategic design of oral gene delivery platforms with potential practical applications in the long term.