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Vaccinations01:51

Vaccinations

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Intradermal Vaccination with PLGA Nanoparticles via Dissolving Microneedles and Classical Injection Needles.

Jihui Lee1, Malene A Neustrup1, Bram Slütter1

  • 1Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333CC, Leiden, the Netherlands.

Pharmaceutical Research
|February 9, 2024
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Summary

This study developed dissolving microneedle arrays (dMNAs) loaded with poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) for enhanced vaccine delivery. Aqueous formulations with PLGA NPs showed superior CD4+ and CD8+ T-cell responses compared to dMNAs in mice.

Keywords:
dissolving microneedleintradermal drug deliverynanoparticlesvaccine formulationvaccine immunogenicity

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Area of Science:

  • Biomaterials Science
  • Immunology
  • Nanotechnology

Background:

  • Dissolving microneedle arrays (dMNAs) offer advantages over conventional needles for vaccine delivery.
  • Incorporating particulate adjuvants like poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) into dMNAs may enhance immune responses.

Purpose of the Study:

  • To prepare PLGA NP-loaded dMNAs.
  • To compare T-cell responses induced by intradermal injection of aqueous-PLGA-NP formulations versus PLGA-NP-loaded dMNAs in mice.

Main Methods:

  • PLGA NPs were prepared using microfluidics, characterized for encapsulation efficiency (ovalbumin and CpG), size, zeta potential, and polydispersity index.
  • PLGA NP-loaded dMNAs were fabricated using centrifugation, with varying formulations assessed for NP integrity.
  • Immunogenicity was evaluated in mice by comparing T-cell responses to dMNA and aqueous formulations containing ovalbumin and CpG, with and without PLGA NPs.

Main Results:

  • PLGA NPs were approximately 100 nm in size.
  • A dMNA formulation with poly(vinyl alcohol) (PVA) maintained PLGA NP integrity and exhibited 100% penetration efficiency and rapid dissolution (<30 min) in ex vivo human skin at a PLGA:PVA ratio of 1:9.
  • Aqueous formulations, both soluble and PLGA NP-based, induced the highest CD4+ T-cell responses in blood and spleen cells.

Conclusions:

  • Successfully fabricated PLGA NP-incorporated dMNAs.
  • Aqueous formulations containing PLGA NPs demonstrated superior induction of CD4+ and CD8+ T-cell responses compared to dMNAs.