Intradermal delivery of vaccine nanoparticles using hollow microneedle array generates enhanced and balanced immune response

Lin Niu, Leonard Y. Chu, Scott A. Burton, Kris J. Hansen, Jayanth Panyam

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Hollow microneedles can help overcome the skin permeation barrier imposed by the stratum corneum and facilitate transcutaneous delivery of nanoparticle delivery systems. In the present study, we investigated the use of the hollow microneedle array for intradermal delivery of polymeric nanoparticles (NPs) in rats. Compared to intravenous and subcutaneous routes of administration, intradermal delivery of polymeric NPs via a hollow microneedle array resulted in a unique pharmacokinetic profile, characterized by an early burst transit through the draining lymph nodes and a relatively limited overall systemic exposure. Based on high local lymphatic concentrations achieved, we investigated the use of this modality for vaccine delivery. A model antigen ovalbumin (OVA) and TLR agonists imiquimod and monophosphoryl Lipid A encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) NPs were used as the vaccine formulation. Compared to soluble OVA-based vaccine, OVA loaded NPs demonstrated faster antibody affinity maturation kinetics. Moreover, antigen loaded NPs delivered via a hollow microneedle array elicited a significantly higher IgG2a antibody response and higher number of interferon (IFN)-γ secreting lymphocytes, both markers of Th1 response, in comparison to antigen loaded NPs delivered by intramuscular injection and soluble antigen delivered through hollow microneedle array. Overall, our results show that hollow microneedle mediated intradermal delivery of polymeric NPs is a promising approach to improve the effectiveness of vaccine formulations.

Original languageEnglish (US)
Pages (from-to)268-278
Number of pages11
JournalJournal of Controlled Release
Volume294
DOIs
StatePublished - Jan 28 2019

Keywords

  • Cancer vaccine
  • Immunotherapy
  • Intradermal delivery
  • Microneedles
  • Nanoparticle
  • TLR7/8 agonist

PubMed: MeSH publication types

  • Journal Article

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