Effective transcutaneous immunization using a combination of iontophoresis and nanoparticles

Bernardi, Daniela Spuri; Bitencourt, Claudia S.; Silveira, Denise Sayuri Calheiros da; Cruz, Estael L.C.M. da; Pereira-da-Silva, Marcelo A.; Faccioli, Lúcia Helena; Lopez, Renata Fonseca Vianna

doi:10.1016/j.nano.2016.07.001

Cited by 44 publications

(17 citation statements)

References 46 publications

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“…Several studies have been performed to assess the use of active delivery methods together with particle-based systems for TCI, i.e., microneedles (17,18,42), iontophoresis (20), jet or powder injection, or mild skin ablation by cyano-acrylate skin surface stripping (CSSS) (43). In some of these studies, the combined approaches for TCI with our without the use of adjuvant(s) were reported to enhance vaccine skin entry, activate the innate immune system, thereby serving as a physical adjuvant, and Model Antigen SIINFEKL/ Imiquimod and, where appropriate, CD40 ligands -Enhanced primary CD8+ and CD4+ T-cell responses and tumor protection when vaccinated with the solid nanoemulsion (SN) in comparison to the reference formulation, Aldara ® -Co-application of the SN with co-stimulatory ligands such as CD40 ligands, promotes specific T-cell responses in the priming and memory phase, strongly enhancing antitumor protection in mice lead to higher or altered levels of humoral and cellular immune responses compared to subcutaneous (SC) or intramuscular (IM) vaccination with particulate or soluble antigens (19).…”

Section: Active Delivery Methodsmentioning

confidence: 99%

Current Progress in Particle-Based Systems for Transdermal Vaccine Delivery

et al. 2020

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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.

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Section: Active Delivery Methodsmentioning

confidence: 99%

Current Progress in Particle-Based Systems for Transdermal Vaccine Delivery

et al. 2020

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“…Polymeric nanoparticles were recently applied to encapsulate immunologic active materials for TCI [21–25]. However, due to poor dermal permeation into the rigid structure, tape stripping or iontophoresis should be combined to facilitate transdermal delivery [21–23, 26]. Besides, adjuvants are necessary to be combined with nanoparticles to generate efficient immune responses [24].…”

Section: Introductionmentioning

confidence: 99%

Size-dependent penetration of nanoemulsions into epidermis and hair follicles: implications for transdermal delivery and immunization

et al. 2017

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Nanoemulsions have been widely applied to dermal and transdermal drug delivery. However, whether and to what depth the integral nanoemulsions can permeate into the skin is not fully understood. In this study, an environment-responsive dye, P4, was loaded into nanoemulsions to track the transdermal translocation of the nanocarriers, while coumarin-6 was embedded to represent the cargoes. Particle size has great effects on the transdermal transportation of nanoemulsions. Integral nanoemulsions with particle size of 80 nm can diffuse into but not penetrate the viable epidermis. Instead, these nanoemulsions can efficiently fill the whole hair follicle canals and reach as deep as 588 μm underneath the dermal surfaces. The cargos are released from the nanoemulsions and diffuse into the surrounding dermal tissues. On the contrary, big nanoemulsions, with mean particle size of 500 nm, cannot penetrate the stratum corneum and can only migrate along the hair follicle canals. Nanoemulsions with median size, e.g. 200 nm, show moderate transdermal permeation effects among the three-size nanoemulsions. In addition, colocalization between nanoemulsions and immunofluorescence labeled antigen-presenting cells was observed in the epidermis and the hair follicles, implying possible capture of nanoemulsions by these cells. In conclusion, nanoemulsions are advantageous for transdermal delivery and potential in transcutaneous immunization.

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“…When applying cathodal iontophoresis in vitro, the amount of OVA delivered by liposomes coupled with AgNPs was enhanced 92‐fold, compared to passive delivery. In vivo transcutaneous immunization and differentiation of immune‐competent cells were successfully induced by this liposome and iontophoresis system …”

Section: Transdermal Delivery Of Protein Therapeutics Used In Conjuncmentioning

confidence: 99%

Recent Advances in the Transdermal Delivery of Protein Therapeutics with a Combinatorial System of Chemical Adjuvants and Physical Penetration Enhancements

Park

Lee

et al. 2020

Advanced Therapeutics

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Since the development of protein‐based therapeutics, research has been underway to deliver protein therapeutics into the systemic circulation and target sites have been actively conducted. Most protein‐based therapeutics require parenteral administration, due to their intrinsic vulnerability and susceptibility to enzyme‐mediated degradation. Among the routes of administration, the transdermal delivery system has been regarded as a promising technique to deliver protein therapeutics, offering the advantages of painless administration, ease of termination, and avoidance of first‐pass metabolism. However, unlike small molecular drugs, protein therapeutics have limited skin penetration, due to their macromolecular and hydrophilic properties. Both cheimcal adjuvants (CAs)‐treatment methods and physical penetration enhancer methods (PPEs) have been utilized to increase skin permeability for protein therapeutics. The CAs, which include chemical penetration enhancers and nanocarriers, permit the protein therapeutics to transport easily into the skin, by modifying the stratum corneum (SC) or fabricating their stable formulation. The PPEs, including iontophoresis, electroporation, and ultrasound, can improve the skin permeability of the therapeutic agent through disrupting the SC. In this review, the techniques of both chemical and physical enhancement methods are introduced and an overview of the latest approaches to the transdermal delivery of protein therapeutics is provided.

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Effective transcutaneous immunization using a combination of iontophoresis and nanoparticles

Cited by 44 publications

References 46 publications

Current Progress in Particle-Based Systems for Transdermal Vaccine Delivery

Current Progress in Particle-Based Systems for Transdermal Vaccine Delivery

Size-dependent penetration of nanoemulsions into epidermis and hair follicles: implications for transdermal delivery and immunization

Recent Advances in the Transdermal Delivery of Protein Therapeutics with a Combinatorial System of Chemical Adjuvants and Physical Penetration Enhancements

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