Cyclodextrin microneedles for the delivery of a nanoparticle-based peptide antigen vaccine.

In recent years, microneedles (MNs) have gained considerable interest in drug formulation due to their non-invasive and patient-friendly nature. Dissolving MNs have emerged as a promising approach to enhance drug delivery across the skin in a painless manner without generating sharp waste and providing the possibility for self-administration. Cyclodextrins, a group of cyclic oligosaccharides, are well-established in pharmaceutical products due to their safety and unique ability to form inclusion complexes with various drug molecules. In this manuscript, we report the development and characterization of dissolving MNs composed of cyclodextrins for intradermal delivery of a cyclodextrin-based nanoparticulate vaccine. Different cyclodextrins were tested and the most promising candidates were fabricated into MNs by micromolding. The MNs' piercing effectiveness and drug permeation across the skin were tested ex vivo. Furthermore, in vivo studies were carried out to assess the skin's tolerance to cyclodextrin-based MNs, and to evaluate the immune response using a model peptide antigen in a mouse model. The data revealed that the MNs were well-tolerated and effective, even leading to dose-sparing effects. This study highlights the potential of cyclodextrin-based dissolving MNs as a versatile platform for intradermal vaccine delivery, providing a compatible matrix for nanoparticulate formulations to enhance immune responses.

3D printing of a controlled urea delivery device for the prevention of tooth decay.

Dental caries is one of the most widespread chronic infectious diseases in the world. It is mainly caused by the production of acid in the biofilm from the bacterial metabolism of carbohydrates. Nowadays, the prevention of caries is mainly based on the use of topical formulations containing fluoride. However, effective fluoride supplementation may not be sufficient in high-risk individuals, leading to the exploration of alternative strategies such as the neutralization of acid in the oral cavity. Urea is hydrolyzed into ammonia by oral bacteria, leading to a local alkalization that may counteract tooth decay. Herein, we report the fabrication of 3D printed personalized dental trays with a local and prolonged release of urea. Composite filaments with tunable urea release kinetics were produced by hot melt extrusion of poly(ε-caprolactone) and poly(vinyl alcohol) or poly(ethylene glycol) blends mixed with urea. The filaments were further used to 3D print by fused deposition modeling objects capable of releasing urea in a sustained and spatially controlled manner. In vitro studies performed in the presence of Streptococcus salivarius demonstrated the ability of urea released from a 3D printed model toothguards to reduce the pH drop induced by carbohydrates. This study showed the potential of urea-loaded devices to reduce cariogenic acidification of the environment surrounding the enamel by delivering urea directly to the tooth surface.