Hydrogel‐Forming Microneedles: Current Advancements and Future Trends

Turner, Joseph G.; White, Leah R; Estrela, Pedro; Leese, Hannah S.

doi:10.1002/mabi.202170003

Cited by 54 publications

(39 citation statements)

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“…International Publisher to facile access to immune cells and the potential to avoid detrimental systemic toxicities [6][7][8]. MNs have also been recently investigated for minimally invasive extraction of interstitial skin fluid (ISF) to permit early detection and clinical monitoring of a wide range of pathologies, including cancer [9][10][11][12][13]. ISF comprises 75% of all extracellular fluid and contains biomarkers that can reflect physiological function and correlate with disease state [14][15][16][17].…”

Section: Ivyspringmentioning

confidence: 99%

Polymeric microneedles enable simultaneous delivery of cancer immunomodulatory drugs and detection of skin biomarkers

Dosta¹,

Puigmal²,

Cryer³

et al. 2023

Theranostics

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Background: Immune-modulating therapies impart positive outcomes in a subpopulation of cancer patients. Improved delivery strategies and non-invasive monitoring of anti-tumor effects can help enhance those outcomes and understand the mechanisms associated with the generation of anti-tumor immune responses following immunotherapy. Methods: We report on the design of a microneedle (MN) platform capable of simultaneous delivery of immune activators and collection of interstitial skin fluid (ISF) to monitor therapeutic responses. While either approach has shown promise, the integration of the therapy and diagnostic arms into one MN platform has hardly been explored before. MNs were synthesized out of crosslinked hyaluronic acid (HA) and loaded with a model immunomodulatory nanoparticle-containing drug, CpG oligodinucleotides (TLR9 agonist), for cancer therapy in melanoma and colon cancer models. The therapeutic response was monitored by longitudinal analysis of entrapped immune cells in the MNs following patch retrieval and digestion. Results: Transdermal delivery of CpG-containing NPs with MNs induced anti-tumor immune responses in multiple syngeneic mouse cancer models. CpG-loaded MNs stimulated innate immune cells and reduced tumor growth. Intravital microscopy showed deposition and spatiotemporal co-localization of CpG-NPs within the tumor microenvironment when delivered with MNs. Analysis of MN-sampled ISF revealed similar immune signatures to those seen in the bulk tumor homogenate, such as increased populations of macrophages and effector T cells following treatment. Conclusions: Our hydrogel-based MNs enable effective transdermal drug delivery into immune cells in the tumor microenvironment, and upon retrieval, enable studying the immune response to the therapy over time. This platform has the theranostic potential to deliver a range of combination therapies while detecting biomarkers.

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Section: Ivyspringmentioning

confidence: 99%

Polymeric microneedles enable simultaneous delivery of cancer immunomodulatory drugs and detection of skin biomarkers

Dosta¹,

Puigmal²,

Cryer³

et al. 2023

Theranostics

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“…sampled a limited dermal ISF volume from rats of 0.84 µL in 1 h. [ 34 ] This may be explained by the nature of the materials used, primarily selected for their biocompatibility, good antimicrobial properties and mechanical strength, to the detriment of high swelling rates and sorption capacities. [ 44 ]…”

Section: Rat Dermal Isf Proteomic Analysismentioning

confidence: 99%

Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

Laszlo

Crescenzo

Nieto-Argüello

et al. 2021

Adv Funct Materials

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The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with ‐omics analyses but remains limited in ISF because of its time‐consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate‐based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate‐based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.

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“…The control of the stability and water absorption of the microneedle devices is desired to tune the release of the active principle . Microneedles obtained from pure SF treated or not treated with methanol present almost the same swelling and stability behavior; these microneedles show minor deformation compared to their initial structures following incubation in PBS for 24 h (Figure ).…”

Section: Results and Discussionmentioning

confidence: 99%

Silk Fibroin/Poly(vinyl Alcohol) Microneedles as Carriers for the Delivery of Singlet Oxygen Photosensitizers

Rojas

Oliveira

Araújo

et al. 2021

ACS Biomater. Sci. Eng.

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Photodynamic therapy (PDT) is a medical treatment in which a combination of a photosensitizing drug and visible light produces highly cytotoxic reactive oxygen species (ROS) that leads to cell death. One of the main drawbacks of PDT for topical treatments is the limited skin penetration of some photosensitizers commonly used in this therapy. In this study, we propose the use of polymeric microneedles (MNs) prepared from silk fibroin and poly(vinyl alcohol) (PVA) to increase the penetration efficiency of porphyrin as possible applications in photodynamic therapy. The microneedle arrays were fabricated from mixtures in different proportions (1:0, 7:3, 1:1, 3:7, and 0:1) of silk fibroin and PVA solutions (7%); the polymer solutions were cast in polydimethylsiloxane (PDMS) molds and dried overnight. Patches containing grids of 10 × 10 microneedles with a square-based pyramidal shape were successfully produced through this approach. The polymer microneedle arrays showed good mechanical strength under compression force and sufficient insertion depth in both Parafilm M and excised porcine skin at different application forces (5, 20, 30, and 40 N) using a commercial applicator. We observe an increase in the cumulative permeation of 5-[4-(2-carboxyethanoyl) aminophenyl]-10,15,20-tris-(4-sulphonatophenyl) porphyrin trisodium through porcine skin treated with the polymer microneedles after 24 h. MNs may be a promising carrier for the transdermal delivery of photosensitizers for PDT, improving the permeation of photosensitizer molecules through the skin, thus improving the efficiency of this therapy for topical applications.

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Hydrogel‐Forming Microneedles: Current Advancements and Future Trends

Cited by 54 publications

References 0 publications

Polymeric microneedles enable simultaneous delivery of cancer immunomodulatory drugs and detection of skin biomarkers

Polymeric microneedles enable simultaneous delivery of cancer immunomodulatory drugs and detection of skin biomarkers

Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

Silk Fibroin/Poly(vinyl Alcohol) Microneedles as Carriers for the Delivery of Singlet Oxygen Photosensitizers

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