Intradermal vaccination with hollow microneedles: A comparative study of various protein antigen and adjuvant encapsulated nanoparticles

Guangsheng Du,Rania M Hathout,Maha Nasr,M Reza Nejadnik,Jing Tu,Roman I Koning,Abraham J Koster,Bram Slütter,Alexander Kros,Wim Jiskoot,Joke A Bouwstra,Juha Mönkäre

doi:10.1016/j.jconrel.2017.09.021

Guangsheng Du, Rania M Hathout + Show 10 more

Open Access

https://doi.org/10.1016/j.jconrel.2017.09.021

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Abstract

In this study, we investigated the potential of intradermal delivery of nanoparticulate vaccines to modulate the immune response of protein antigen using hollow microneedles. Four types of nanoparticles covering a broad range of physiochemical parameters, namely poly (lactic-co-glycolic) (PLGA) nanoparticles, liposomes, mesoporous silica nanoparticles (MSNs) and gelatin nanoparticles (GNPs) were compared. The developed nanoparticles were loaded with a model antigen (ovalbumin (OVA)) with and without an adjuvant (poly(I:C)), followed by the characterization of size, zeta potential, morphology, and loading and release of antigen and adjuvant. An in-house developed hollow-microneedle applicator was used to inject nanoparticle suspensions precisely into murine skin at a depth of about 120μm. OVA/poly(I:C)-loaded nanoparticles and OVA/poly(I:C) solution elicited similarly strong total IgG and IgG1 responses. However, the co-encapsulation of OVA and poly(I:C) in nanoparticles significantly increased the IgG2a response compared to OVA/poly(I:C) solution. PLGA nanoparticles and liposomes induced stronger IgG2a responses than MSNs and GNPs, correlating with sustained release of the antigen and adjuvant and a smaller nanoparticle size. When examining cellular responses, the highest CD8+ and CD4+ T cell responses were induced by OVA/poly(I:C)-loaded liposomes. In conclusion, the applicator controlled hollow microneedle delivery is an excellent method for intradermal injection of nanoparticle vaccines, allowing selection of optimal nanoparticle formulations for humoral and cellular immune responses.

Highlights

Skin is an attractive administration site for immunization and may act as an excellent alternative for traditional intramuscular or subcutaneous vaccination
The electron microscopy images revealed a spherical shape of poly (lactic-co-glycolic) acid (PLGA) nanoparticles, liposomes and gelatin nanoparticles (GNPs), whereas mesoporous silica nanoparticles (MSNs) had a rectangular shape with mesochannels along the short axis (Fig. 1)
The estimated size based on electron microscopy images is consistent with the size in Table 1 for PLGA nanoparticles and liposomes

Summary

Introduction

Skin is an attractive administration site for immunization and may act as an excellent alternative for traditional intramuscular or subcutaneous vaccination. The uppermost layer of the skin, the stratum corneum, is the main barrier that prevents the transport of vaccines (> 500 Da) across the skin. Novel delivery methods need to be developed. Among various methods developed for antigen delivery via the skin, especially microneedle-based approaches have recently attracted increasing attention [2]. The major advantage of microneedles is their ability to pierce the skin in a minimally invasive manner and subsequently deliver their payload in the superficial skin layers potentially without pain, owing to the limited penetration depth of microneedles (typically < 500 μm) [3]

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