Coated microneedles for transdermal delivery of a potent pharmaceutical peptide

Kapoor, Yash; Milewski, Mikolaj; Dick, Lisa; Zhang, Jingtao; Bothe, Jameson R.; Gehrt, Michele; Manser, Kim; Nissley, Becky; Petrescu, Ioan; Johnson, Peter; Burton, Scott A.; Moseman, Joan; Hua, Vinh; Grunewald, Tonya; Tomai, Mark A.; Smith, Ronald L.

doi:10.1007/s10544-019-0462-1

Cited by 42 publications

(29 citation statements)

References 18 publications

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“…One advantage of coated MN systems compared to liquid formulations is enhanced stability of the dried form of the active pharmaceutical ingredient (Kapoor et al 2019).…”

Section: Discussionmentioning

confidence: 99%

“…The stability of a number of MN-coated therapeutics, including insulin (Pere et al 2018), have been studied and published data indicates stability times from weeks to months (Peters et al 2012;Kim et al 2015;Baek et al 2017;Kapoor et al 2019). In this study, PI coating formulations were freshly prepared and MNs were coated within hours of their use but future studies should evaluate the physical and chemical stability of the system in controlled conditions for extended storage times.…”

Section: Discussionmentioning

confidence: 99%

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

Arikat

Hanna

Singh

et al. 2020

Journal of Controlled Release

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Antigen-specific immunotherapy (ASI) has been proposed as an alternative treatment strategy for type 1 diabetes (T1D). ASI aims to induce a regulatory, rather than stimulatory, immune response in order to reduce, or prevent, autoimmune mediated β-cell destruction, thus preserving endogenous insulin production. The abundance of immunocompetent antigen presenting cells (APCs) within the skin makes this organ an attractive target for immunotherapies. Microneedles (MNs) have been proposed as a suitable drug delivery system to facilitate intradermal delivery of autoantigens in a minimally invasive manner. However, studies to date have employed single peptide autoantigens, which would restrict ASI to patients expressing specific Human Leukocyte Antigen (HLA) molecules, thus stratifying the patient population. This study aims to develop, for the first time, an intradermal MN delivery system to target proinsulin, a large multi-epitope protein capable of inducing tolerance in a heterogenous (in terms of HLA status) population of T1D patients, to the immunocompetent cells of the skin. An optimized three component coating formulation containing proinsulin, a diluent and a surfactant, facilitated uniform and reproducible coating of >30μg of the active pharmaceutical ingredient on a stainless steel MN array consisting of thirty 500μm projections. When applied to a murine 2 model these proinsulin-coated MNs efficiently punctured the skin and after a limited insertion time (150 seconds) a significant proportion of the therapeutic payload (86%) was reproducibly delivered into the local tissue. Localized delivery of proinsulin in non-obese diabetic (NOD) mice using the coated MN system stimulated significantly greater proliferation of adoptively transferred antigen-specific CD8+ T cells in the skin draining lymph nodes compared to a conventional intradermal injection. This provides evidence of targeted delivery of the multi-epitope proinsulin antigen to skinresident APCs, in vivo, in a form that enables antigen presentation to antigen-specific T cells in the local lymph nodes. The development of an innovative coated MN system for highly targeted and reproducible delivery of proinsulin to local immune cells warrants further evaluation to determine translation to a tolerogenic clinical outcome.

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“…One advantage of coated MN systems compared to liquid formulations is enhanced stability of the dried form of the active pharmaceutical ingredient (Kapoor et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Arikat

Hanna

Singh

et al. 2020

Journal of Controlled Release

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“…[ 230 ] for delivery of desmopressin. Subsequently, this type of MN has been used for enhancing the delivery of other macromolecules, such as insulin [ 254 ], deoxyribonucleic acid (DNA) [ 255 ], exendin-4 [ 256 ], botulinum toxin-A [ 257 ] and peptide-A [ 258 ]. Furthermore, the use of coated MN has also been reported for delivery of lidocaine [ 259 ] and riboflavin [ 260 ].…”

Section: Microneedlesmentioning

confidence: 99%

“…16 Coated MN with different drug coatings: (a) Desmopressin (reproduced with permission from [230] Copyright 2004, Elsevier). (b) DNA (reprinted with permission from [255] Copyright © 2010, American Chemical Society) used for enhancing the delivery of other macromolecules, such as insulin [254], deoxyribonucleic acid (DNA) [255], exendin-4 [256], botulinum toxin-A [257] and peptide-A [258]. Furthermore, the use of coated MN has also been reported for delivery of lidocaine [259] and riboflavin [260].…”

Section: Coated Microneedlesmentioning

confidence: 99%

Enhancement strategies for transdermal drug delivery systems: current trends and applications

Ramadon

McCrudden

Courtenay

et al. 2021

Drug Deliv. and Transl. Res.

234

159

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Transdermal drug delivery systems have become an intriguing research topic in pharmaceutical technology area and one of the most frequently developed pharmaceutical products in global market. The use of these systems can overcome associated drawbacks of other delivery routes, such as oral and parenteral. The authors will review current trends, and future applications of transdermal technologies, with specific focus on providing a comprehensive understanding of transdermal drug delivery systems and enhancement strategies. This article will initially discuss each transdermal enhancement method used in the development of first-generation transdermal products. These methods include drug/vehicle interactions, vesicles and particles, stratum corneum modification, energy-driven methods and stratum corneum bypassing techniques. Through suitable design and implementation of active stratum corneum bypassing methods, notably microneedle technology, transdermal delivery systems have been shown to deliver both low and high molecular weight drugs. Microneedle technology platforms have proven themselves to be more versatile than other transdermal systems with opportunities for intradermal delivery of drugs/biotherapeutics and therapeutic drug monitoring. These have shown that microneedles have been a prospective strategy for improving transdermal delivery systems. Graphical abstract

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“…In the second case, the “ coat and poke ” mechanism involves the coating of solid MNs with a suitable drug formulation, so that when applied to the skin, the drug continuously dissolves and deposits, after which MNs are withdrawn ( Figure 1 C). This type of MN is a single-unit drug delivery system, which serves as a puncturing skin device and drug reservoir [ 37 ] for a wide range of drugs, including both hydrophilic or hydrophobic drugs with low molecular weight, nucleic acids [ 43 ], proteins [ 74 ], peptides [ 75 , 76 ], or particles. A major obstacle to this approach is the limited quantities of the drug that can be applied on MN bases and shafts [ 6 , 37 ], as thick coatings, due to the reduced sharpness of MNs, lead to poor drug delivery efficiency into the skin.…”

Section: Microneedles: Characteristics Classification and Delivery Strategiesmentioning

confidence: 99%

3D Printing—A “Touch-Button” Approach to Manufacture Microneedles for Transdermal Drug Delivery

et al. 2021

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Microneedles (MNs) represent the concept of attractive, minimally invasive puncture devices of micron-sized dimensions that penetrate the skin painlessly and thus facilitate the transdermal administration of a wide range of active substances. MNs have been manufactured by a variety of production technologies, from a range of materials, but most of these manufacturing methods are time-consuming and expensive for screening new designs and making any modifications. Additive manufacturing (AM) has become one of the most revolutionary tools in the pharmaceutical field, with its unique ability to manufacture personalized dosage forms and patient-specific medical devices such as MNs. This review aims to summarize various 3D printing technologies that can produce MNs from digital models in a single step, including a survey on their benefits and drawbacks. In addition, this paper highlights current research in the field of 3D printed MN-assisted transdermal drug delivery systems and analyzes parameters affecting the mechanical properties of 3D printed MNs. The current regulatory framework associated with 3D printed MNs as well as different methods for the analysis and evaluation of 3D printed MN properties are outlined.

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Coated microneedles for transdermal delivery of a potent pharmaceutical peptide

Cited by 42 publications

References 18 publications

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

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

Enhancement strategies for transdermal drug delivery systems: current trends and applications

3D Printing—A “Touch-Button” Approach to Manufacture Microneedles for Transdermal Drug Delivery

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