Current Progress in Particle-Based Systems for Transdermal Vaccine Delivery

Abstract

Transcutaneous immunization (TCI) via needle-free and non-invasive drug delivery systems is a promising approach for overcoming the current limitations of conventional parenteral vaccination methods. The targeted access to professional antigen-presenting cell (APC) populations within the skin, such as Langerhans cells (LCs), various dermal dendritic cells (dDCs), macrophages, and others makes the skin an ideal vaccination site to specifically shape immune responses as required. The stratum corneum (SC) of the skin is the main penetration barrier that needs to be overcome by the vaccine components in a coordinated way to achieve optimal access to dermal APC populations that induce priming of T-cell or B-cell responses for protective immunity. While there are numerous approaches to penetrating the SC, such as electroporation, sono-or iontophoresis, barrier and ablative methods, jet and powder injectors, and microneedle-mediated transport, we will focus this review on the recent progress made in particle-based systems for TCI. This particular approach delivers vaccine antigens together with adjuvants to perifollicular APCs by diffusion and deposition in hair follicles. Different delivery systems including nanoparticles and lipid-based systems, for example, solid nano-emulsions, and their impact on immune cells and generation of a memory effect are discussed. Moreover, challenges for TCI are addressed, including timely and targeted delivery of antigens and adjuvants to APCs within the skin as well as a deeper understanding of the ill-defined mechanisms leading to the induction of effective memory responses.

Emerging skin-targeted drug delivery strategies to engineer immunity: A focus on infectious diseases

“…These innovative vaccine-loaded systems have been shown to enhance the immunogenicity of antigens through several different mechanisms, including mimicking pathogens, triggering innate signaling pathways, protecting vaccines from in vivo degradation, improving uptake by APCs, or sustaining the presence of antigens, with or without adjuvants [234][235][236][237]. Although these particulate vaccine systems have been predominantly administered by traditional parenteral injections, they have also synergized with MNAs (e.g., Figure 3) for minimally invasive skin-targeted delivery for efficacious immunization [238][239][240][241].…”

Microneedles for painless transdermal immunotherapeutic applications

“…The presence of LCs in the epidermal layer makes them the first line of APCs that meet skin-invading antigens. This opens up a new avenue for immunotherapy of diseases without causing noticeable adverse effects [180]. For example, Burg et al designed microprojection arrays (MPA) in polycarbonate material through a hot embossing procedure and coated OVA onto the surface of the MPAs [181].…”

Technological Approaches for Improving Vaccination Compliance and Coverage

“…The aforementioned physical devices, although efficient in antigen delivery into the skin, may lead to some skin barrier damage, making them less suitable for mass vaccination under critical hygienic conditions [108,109]. As a result, there has been an increasing interest in passive delivery strategies, particularly nanocarriers, enabling antigen application to intact skin as well as improved antigen stability, sustained antigen release and increased antigenicity by mimicking the size of microorganisms [108,110,111]. Until now, different nanoparticles have been studied for this purpose, including vesicular nanocarriers (transfersomes, ethosomes, liposomes, niosomes, nanoemulsions) and solid nanoparticles (polymeric nanoparticles, silica-based nanoparticles) [92,110].…”

“…Until now, different nanoparticles have been studied for this purpose, including vesicular nanocarriers (transfersomes, ethosomes, liposomes, niosomes, nanoemulsions) and solid nanoparticles (polymeric nanoparticles, silica-based nanoparticles) [92,110]. However, although nanoparticles may lead to a superior immune response compared to conventional intramuscular immunisation (particularly with an appropriate adjuvant), progress towards clinical settings has been negligible, due to difficulties in ensuring the accurate, reproducible and efficient delivery of antigen-loaded nanoparticles into the epidermal and dermal tissue [109,111]. Interestingly, in recent years, vaccination via the follicular route using nanoparticles, particularly non-flexible ones, has been recognised as a promising approach.…”