Skin Dendritic Cell Targeting via Microneedle Arrays Laden with Antigen-Encapsulated Poly-d,l-lactide-co-Glycolide Nanoparticles Induces Efficient Antitumor and Antiviral Immune Responses

Abstract

The efficacious delivery of antigens to antigen-presenting cells (APCs), in particular, to dendritic cells (DCs), and their subsequent activation remains a significant challenge in the development of effective vaccines. This study highlights the potential of dissolving microneedle (MN) arrays laden with nanoencapsulated antigen to increase vaccine immunogenicity by targeting antigen specifically to contiguous DC networks within the skin. Following in situ uptake, skin-resident DCs were able to deliver antigen-encapsulated poly-d,l-lactide-co-glycolide (PGLA) nanoparticles to cutaneous draining lymph nodes where they subsequently induced significant expansion of antigen-specific T cells. Moreover, we show that antigen-encapsulated nanoparticle vaccination via microneedles generated robust antigen-specific cellular immune responses in mice. This approach provided complete protection in vivo against both the development of antigen-expressing B16 melanoma tumors and a murine model of para-influenza, through the activation of antigen-specific cytotoxic CD8+ T cells that resulted in efficient clearance of tumors and virus, respectively. In addition, we show promising findings that nanoencapsulation facilitates antigen retention into skin layers and provides antigen stability in microneedles. Therefore, the use of biodegradable polymeric nanoparticles for selective targeting of antigen to skin DC subsets through dissolvable MNs provides a promising technology for improved vaccination efficacy, compliance, and coverage.

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

“…However, in these studies using microneedles none of the vaccine antigens were encapsulated in nanoparticles. In one study, dissolving microneedles loaded with PLGA nanoparticle encapsulated antigens were used for intradermal vaccination, and shown to induce a robust antigen-specific protective cellular immune response in mice [24].…”

“…However, relatively little is known about how encapsulation in PLGA nanoparticles modifies T cell responses to antigen/adjuvant combinations that are delivered intradermally by different novel types of microneedles. One recent study reported that PLGA nanoparticles, delivered intradermally using dissolving microneedles arrays [24], induced cellular immune responses and protection against viral infection and tumor growth.…”

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

“…Nanoparticles can also be delivered subcutaneously by intradermal injection [157], epidermal electroporation [158] or via microneedles [159] but also as topical applications using hydrogel scaffolds or patches [154].…”

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant

“…This approach to intradermal vaccination offers better patient compliance, reliability, and simplicity. [8][9][10][11] In this study, the model antigen ovalbumin (OVA) and the adjuvant PD were loaded into liposomes to facilitate uptake of the vaccine by DCs and to reduce the toxicity of the adjuvant. The uptake behavior and toxicity of the OVA-and PD-loaded liposomes (OVA-PD-Lipos) were evaluated using cultured mouse bone marrow dendritic cells (BMDCs), and their hemolytic activity was evaluated in rabbit red blood cells (RBCs).…”