Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA...

Area of Science:

• Biomaterials Science
• Vaccinology
• Nanotechnology

Background:

• DNA vaccines offer broad therapeutic potential but suffer from low in vivo immunogenicity.
• Lack of effective delivery systems hinders DNA vaccine efficacy due to degradation and poor transfection.
• Dissolvable microneedles are a promising technology for improved DNA vaccine delivery and stability.

Purpose of the Study:

• To evaluate four different polymers for formulating DNA-loaded dissolvable microneedles.
• To assess the impact of complexing DNA with the RALA peptide on microneedle formulation and DNA delivery.
• To compare the efficacy of DNA-loaded microneedles using different polymer matrices and RALA complexation.

Main Methods:

• Formulation of DNA-loaded dissolvable microneedles using four distinct polymer matrices.
• Complexation of DNA with a cationic peptide (RALA) before incorporation into microneedle matrices.
• Assessment of DNA integrity, recovery, and in vitro transfection efficiencies of released DNA/RALA nanoparticles.

Main Results:

• Polyvinyl alcohol (PVA) matrices preserved DNA integrity, unlike polyvinylpyrrolidone (PVP) matrices.
• Complexation with RALA enhanced DNA recovery from microneedles and improved in vitro transfection.
• RALA/DNA nanoparticles released from PVA microneedles showed up to 10-fold higher transfection efficiency compared to those from PVP.

Conclusions:

• PVA is a superior polymer matrix for formulating DNA-loaded dissolvable microneedles compared to PVP.
• RALA complexation significantly enhances DNA recovery and transfection efficiency from dissolvable microneedles.
• Dissolvable PVA microneedles loaded with RALA/DNA complexes represent a promising strategy for effective DNA vaccination.