Therapeutic intradermal delivery of tumor necrosis factor-alpha antibodies using tip-loaded dissolvable microneedle arrays

Korkmaz, Emrullah; Friedrich, Emily E.; Ramadan, Mohamed H.; Erdö́s, G.; Mathers, Alicia R.; Özdoğanlar, O. Burak; Washburn, Newell R.; Falo, Louis D.

doi:10.1016/j.actbio.2015.05.036

Cited by 71 publications

(33 citation statements)

References 40 publications

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“…Therefore, the characterization of cellular responses to soluble cell-signaling molecules and to their gradients is of great importance for understanding how multicellular collective behaviors are organized and regulated. Understanding the roles of gradient sensing in disease also guides us toward novel therapies including regenerative stem cell therapy for neural injury, localized drug delivery for immunomodulation of inflammatory diseases [10] and T-cell engineering for the immunotherapy of cancer [11].…”

Section: Introductionmentioning

confidence: 99%

Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers

et al. 2020

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Gradients of soluble molecules coordinate cellular communication in a diverse range of multicellular systems. Chemokine-driven chemotaxis is a key orchestrator of cell movement during organ development, immune response and cancer progression. Chemotaxis assays capable of examining cell responses to different chemokines in the context of various extracellular matrices will be crucial to characterize directed cell motion in conditions which mimic whole tissue conditions. Here, a microfluidic device which can generate different chemokine patterns in flow-free gradient chambers while controlling surface extracellular matrix (ECM) to study chemotaxis either at the population level or at the single cell level with high resolution imaging is presented. The device is produced by combining additive manufacturing (AM) and soft lithography. Generation of concentration gradients in the device were simulated and experimentally validated. Then, stable gradients were applied to modulate chemotaxis and chemokinetic response of Jurkat cells as a model for T lymphocyte motility. Live imaging of the gradient chambers allowed to track and quantify Jurkat cell migration patterns. Using this system, it has been found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. The chemotaxis of the Jurkat cells was also found to be governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Distinct migratory behaviors in response to chemokine gradients in different contexts may be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Our approach demonstrates the feasibility of using a flow-free gradient chamber for evaluating cross-regulation of cell motility by multiple factors in different biologic processes.

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Section: Introductionmentioning

confidence: 99%

Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers

et al. 2020

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“…Korkmaz et al developed a kind of DMN loaded with anti-TNF-a Ab in the tips of the needles and found that this method demonstrated powerful delivery efficacy and anti-inammation function in BLAB/c mice with psoriatic lesions induced by imiquimod. 52 The MNP, fabricated using low viscosity sodium carboxymethyl cellulose, has a complete appearance and completely dissolved in 30 minutes with the help of an applicator. In a murine psoriasis model, the MNP was observed to have the ability to reduce inammation from the aspects of epidermal thickness, cellular inltrate, and IL-1b mRNA expression.…”

Section: Application Of Microneedles In Psoriasismentioning

confidence: 99%

Microneedles: a potential strategy in transdermal delivery and application in the management of psoriasis

2020

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“…A few weeks ago, two studies showing immunogenicity of a plasmid DNA or adenovirus (serotype 52) expressing virus-like particles in mice and non-human primates were published Abbink et al, 2016). Here, to build on these initial findings to develop an effective ZIKV vaccine, we describe the development of a recombinant adenoviral vector expressing codon-optimized ZIKV E antigen and a subunit recombinant ZIKV E vaccine delivered transcutaneously by carboxymethyl cellulose (CMC) microneedle arrays (MNAs) (Bediz et al, 2014;Korkmaz et al, 2015), investigate their ability to induce neutralizing immune responses, and assess their ability to passively protect against ZIKV challenge in a novel neonatal ZIKV infection mouse model.…”

Section: Introductionmentioning

confidence: 99%

Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

et al. 2016

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Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.

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Therapeutic intradermal delivery of tumor necrosis factor-alpha antibodies using tip-loaded dissolvable microneedle arrays

Cited by 71 publications

References 40 publications

Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers

Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers

Microneedles: a potential strategy in transdermal delivery and application in the management of psoriasis

Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

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