Targeting proinsulin to local immune cells using an intradermal microneedle delivery system; a potential antigen-specific immunotherapy for type 1 diabetes

Arikat, Farah; Hanna, Stephanie; Singh, Ravinder; Vilela, Luciano; Wong, F. Susan; Dayan, Colin; Coulman, Sion; Birchall, James Caradoc

doi:10.1016/j.jconrel.2020.02.031

Cited by 27 publications

(24 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In preclinical T1D, stainless steel MNs coated with proinsulin delivered %86% of the therapy into local issue of a NOD mouse model (Figure 5A). [133] Proinsulincoated MNs increased the frequency of proinsulin specific T cells Figure 4. Carrier-free systems concentrate immune cues to APCs without intrinsic inflammatory effects.…”

Section: Mns Deliver Antigen and Immunomodulatory Cues To Skin-reside...mentioning

confidence: 99%

“…To address these limitations and exploit the advantages of ID and TD delivery, MNs are emerging as alternatives for ASIT delivery. [133][134][135][136][137][138] MNs efficiently access concentrated APCs in the skin niche, which can then drive their activation and presentation of antigen to T cells for tolerance induction. MNs are tiny needles usually in the range of 25-500 μm that delivers therapeutic drugs through skin.…”

Section: Mns Deliver Antigen and Immunomodulatory Cues To Skin-reside...mentioning

confidence: 99%

See 1 more Smart Citation

Delivery Route Considerations for Designing Antigen‐Specific Biomaterial Strategies to Combat Autoimmunity

Ackun-Farmmer

Jewell

2023

Advanced NanoBiomed Research

View full text Add to dashboard Cite

Motivating the Development of Antigen-Specific ImmunotherapiesAutoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CD), and many others develop when the immune system mistakenly recognizes self-antigens as foreign, resulting in an orchestrated attack of host tissues. MS is a demyelinating disease that affects the central nervous system (CNS), RA is a chronic inflammatory joint disorder that can affect other tissues and organs, and T1D is a chronic condition whereby the pancreas produces little or no insulin. Complications from T1D can impact other tissues and organs. CD is a chronic digestive autoimmune disease that is triggered by gluten consumption, resulting in damage to the small intestine. The exact causes of autoimmune diseases are only partially understood. However, biological sex, [1,2] genetics, [3,4] existing autoimmune disease, [5] lifestyle (i.e., smoking, obesity, and exposure), [6][7][8][9][10][11] certain medications, [12] and certain infections [13][14][15][16][17] have been linked with the development of autoimmune diseases. For example, most autoimmune diseases affect more female than male patients, but the reason for this bias is unclear. [1] In MS, risk gene variant, HLA-DRB1*15:01, increases risk for patients, [18] and infection by Epstein-Barr virus (EBV) is associated with increased risks of MS, RA, and other autoimmune diseases. [13][14][15] These are currently no cures for these diseases, creating chronic battles that affect patient quality of life and require life-long compliance. Owing to the complex immunopathology of autoimmune disease, current treatments, even monoclonal antibodies, are not able to distinguish between normal and self-reactive cells. These therapies exploit distinct parenteral (e.g., intravenous [IV], subcutaneous [S.C.], intramuscular (IM), intradermal (ID), transdermal, intranodal) or mucosal (e.g., oral, intranasal (IN), pulmonary, sublingual, ocular) delivery routes to reduce disease severity. [19][20][21][22][23] For example, Ocrelizumab (Ocrevus, Genentech), a recombinant antibody that binds to CD20 on B lymphocytes to treat MS, is administered via IV injection and associated with risk of infections and allergic responses in certain patients. [19] Methotrexate, a first-line disease-modifying antirheumatic drug, is provided orally or S.C. but can lead to liver and lung damage and

show abstract

Section: Mns Deliver Antigen and Immunomodulatory Cues To Skin-reside...mentioning

confidence: 99%

Section: Mns Deliver Antigen and Immunomodulatory Cues To Skin-reside...mentioning

confidence: 99%

Delivery Route Considerations for Designing Antigen‐Specific Biomaterial Strategies to Combat Autoimmunity

Ackun-Farmmer

Jewell

2023

Advanced NanoBiomed Research

View full text Add to dashboard Cite

show abstract

“…[117][118][119][120] In one preliminary study looking at the uptake of pro-insulin, coated stainless steel microneedle delivery was shown to elicit greater antigen-specific activation of cells compared to intradermal injection due to the sustained release from the needles. [121] In a separate study, insoluble T1D autoantigen was conjugated to naturally suppressive gold NPs (Figure 6D), and actively injected into the skin with microneedles. [122,123] In a highly clinically relevant model of ex vivo human skin, gold NPs with peptide were readily taken up by DCs and suppressed activation of antigen specific CD4 T cells in a dose-dependent manner.…”

Section: Materials Enable Direct Targeting Of Skin-resident Immune Ce...mentioning

confidence: 99%

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

2023

View full text Add to dashboard Cite

Autoimmunity and allergies affect a large number of people across the globe. Current approaches to these diseases target cell types and pathways that drive disease, but these approaches are not cures and cannot differentiate between healthy cells and disease‐causing cells. New immunotherapies that induce potent and selective antigen‐specific tolerance is a transformative goal of emerging treatments for autoimmunity and serious allergies. These approaches offer the potential of halting—or even reversing—disease, without immunosuppressive side effects. However, translating successful induction of tolerance to patients is unsuccessful. Biomaterials offer strategies to direct and maximize immunological mechanisms of tolerance through unique capabilities such as codelivery of small molecules or signaling molecules, controlling signal density in key immune tissues, and targeting. While a growing body of work in this area demonstrates success in preclinical animal models, these therapies are only recently being evaluated in human trials. This review will highlight the most recent advances in the use of materials to achieve antigen‐specific tolerance and provide commentary on the current state of the clinical development of these technologies.

show abstract

“…Following this concept, Arikat et al developed Proinsulin (PI)-coated MNs to transport PI protein into the superficial layers of the skin, targeting immature epidermal Langerhans cells (LCs) and steady-state DCs, which exhibit tolerogenic functions [142]. The presence of polysorbate 80 as a non-ionic surfactant in the coating formulation resulted in the uniform coating of protein onto the outer surface of MNs.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Microneedles for painless transdermal immunotherapeutic applications

Amani

Shahbazi

D'Amico

et al. 2021

Journal of Controlled Release

165

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Targeting proinsulin to local immune cells using an intradermal microneedle delivery system; a potential antigen-specific immunotherapy for type 1 diabetes

Cited by 27 publications

References 81 publications

Delivery Route Considerations for Designing Antigen‐Specific Biomaterial Strategies to Combat Autoimmunity

Delivery Route Considerations for Designing Antigen‐Specific Biomaterial Strategies to Combat Autoimmunity

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps

Microneedles for painless transdermal immunotherapeutic applications

Contact Info

Product

Resources

About