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

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.

Diverse Mechanisms of Allergen Specific Immunotherapy

“…This study showed that nanoparticles coated with poly lactic-co-glycolic acid (PLGA) induced a stronger IgG2a response than mesoporous silica nanoparticles, gelatin nanoparticles and liposomes. Moreover, CD8 + and CD4 + T cell responses were highest when induced by OVA/poly(I:C)loaded liposomes [28]. In summary, a microneedle delivery method was suggested for the intradermal injection of nanoparticle vaccines.…”

“…In summary, a microneedle delivery method was suggested for the intradermal injection of nanoparticle vaccines. This novel antigen administration approach was tested in murine models [28]. However, it may induce tolerance more efficiently in human compared to other administration routes.…”

Progress in Microneedle-Mediated Protein Delivery

“…Antigen co-encapsulated with adjuvant induced antibody responses in a more effective way compared with the free OVA/adjuvant. This demonstrated that hollow MNs accompanied by the applicator are a promising tool for intradermal vaccination [74]. Using the same liposome composition and the co-encapsulation of diphtheria toxoid and adjuvant, it was demonstrated that cationic liposome is able to initiate strong immune responses.…”

A Temperature Resistant Extracts Prepared from the Perinereis aibuhitensis and Its Antioxidative Characterization

“…Much attention has been focused on the P. aibuhitensis in recent years because several bioactive components have been identified from P. aibuhitensis including antimicrobial peptide (Pan, 2004), glycerophospholipids (Hirobe et al, 2015) and protease (Li et al, 2006), etc. Owing to P. aibuhitensis good adaptability to stressful environmental conditions, some researchers have regarded them as biochemical responses to specific pollutants as well as potentially ecological keystone species for monitoring programs (Perez, Blasco, & Sole, 2004).…”

“…Among free radicals, reactive oxygen species such as hydrogen peroxide (H 2 O 2 ), hydroxyl radical (OH), and superoxide anion (O 2) are usually generated during cellular metabolism (Yuan, Chen, Zhou, Liu, & Yang, 2010). Hydroxyl radical is a neutral form from hydroxide ion and has a high reactivity, making it a very dangerous radical to the human cells (Du et al, 2017). Superoxide anion, a primary species of reactive oxygen species (ROS) function as a defense against viral or bacterial attack, also lead to damage of proteins, DNA, and lipid structures in human body (Tian, Mao, Okajima, & Ohsaka, 2005;Wang et al, 2013).…”