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Pharmaceutics
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Microarray Patches for Transdermal Drug Delivery
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Microarray Patches for Transdermal Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 10 January 2025 | Viewed by 13243

Special Issue Editors

Dr. Ana Sara Cordeiro

E-Mail Website
Guest Editor
Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK
Interests: drug delivery; controlled release; nanomedicine; vaccine delivery; transdermal delivery; microneedles; diagnostics
Special Issues, Collections and Topics in MDPI journals
Dr. Aaron Hutton

E-Mail Website
Guest Editor
School of Pharmacy, Queen’s University Belfast, Belfast, UK
Interests: drug delivery; microarray patches; nanosuspensions; biotherapeutics; clinical translation

Special Issue Information

Dear Colleagues,

Nearly 25 years on from the publication of the first paper on microarray patch-mediated drug delivery, the field is now tantalisingly close to achieving a commercial product. The World Economic Forum for instance has listed microarray patches as one of the Top Ten Emerging Technologies in 2020. This is owing to the number of advantages microarray patches can offer over the current routes of drug administration, such as the ability to avoid first-pass metabolism and gastrointestinal degradation, pain-free administration and avoidance of needle-stick injuries common with hypodermic syringes. To date, the transdermal delivery of both small and large molecules for therapeutic applications has been investigated using hollow, coated, dissolving, hydrogel-forming and porous microarray patch designs. Therefore, the aim of this Special Issue is to provide insights into the current and future developments of microarray patch-mediated transdermal drug delivery and how this can truly achieve patient and commercial benefits. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) scalable manufacturing methods to aid commercialisation, delivery of biologics, development approaches to achieve long-acting transdermal drug delivery, end-user considerations and product designs.

We look forward to receiving your contributions.

Dr. Ana Sara Cordeiro
Dr. Aaron Hutton
Guest Editors

Manuscript Submission Information

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Keywords

  • microarray patches
  • manufacturing methods
  • biotherapeutic agents
  • long-acting transdermal drug delivery
  • end-user microarray patch designs

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Published Papers (7 papers)

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Research

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20 pages, 10346 KiB  
Article
Preparation and In Vitro/In Vivo Characterization of Mixed-Micelles-Loaded Dissolving Microneedles for Sustained Release of Indomethacin
by Baojie Wang, Langkun Liao, Huihui Liang, Jiaxin Chen and Yuqin Qiu
Pharmaceutics 2024, 16(12), 1505; https://doi.org/10.3390/pharmaceutics16121505 - 22 Nov 2024
Viewed by 407
Abstract
Background/Objectives: Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to [...] Read more.
Background/Objectives: Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to improve and sustain transdermal drug delivery. Methods: Indomethacin-loaded mixed micelles (IDM-MMs) were prepared from Soluplus® and Poloxamer F127 by means of a thin-film hydration method. The MMs-loaded DMNs were fabricated using a two-step molding method and evaluated for storage stability, insertion ability, in vitro release, in vitro transdermal penetration, and in vivo PK/PD studies. Results: The obtained MMs were stable at 4 °C and 30 °C for 60 days. The in vitro IDM transdermal penetration was remarkably improved by the MMs-loaded DMNs compared to a commercial patch. A pharmacokinetic study demonstrated that the MMs-loaded DMNs had a relative bioavailability of 4.1 in comparison with the commercial patch. Furthermore, the MMs-loaded DMNs showed a significantly shorter lag time than the commercial patch, as well as a more stable plasma concentration than the DMNs without MMs. The therapeutic efficacy of the IDM DMNs was examined in Complete Freund’s Adjuvant-induced arthritis mice. The IDM DMN treatment effectively reduced arthritis severity, resulting in decreased paw swelling, arthritis index, spleen hyperplasia, and serum IL-1β and TNF-α levels. Conclusions: Our findings demonstrated that the novel MMs-loaded DMNs were an effective strategy for sustained IDM release, providing an alternate route of anti-inflammatory drug delivery. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
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9 pages, 3952 KiB  
Communication
Mechanical Characterization of Individual Needles in Microneedle Arrays: Factors Affecting Compression Test Results
by Yusuke Tsuboko, Hideyuki Sakoda, Yoshihiro Okamoto, Yusuke Nomura and Eiichi Yamamoto
Pharmaceutics 2024, 16(11), 1480; https://doi.org/10.3390/pharmaceutics16111480 - 20 Nov 2024
Viewed by 500
Abstract
Background: This study aims to investigate the impact of test conditions on the results of the compression testing of microneedle arrays (MNAs). Methods: Uniaxial compression tests were conducted on polyglycolic acid-fabricated biodegradable MNAs. Load–displacement curves were obtained for varying conditions, including the number [...] Read more.
Background: This study aims to investigate the impact of test conditions on the results of the compression testing of microneedle arrays (MNAs). Methods: Uniaxial compression tests were conducted on polyglycolic acid-fabricated biodegradable MNAs. Load–displacement curves were obtained for varying conditions, including the number of microneedles (MNs) compressed simultaneously, compression speeds, and compression angles. Subsequently, the buckling load and stiffness were calculated, and the MN deformation during compression was observed. Results: The buckling load and stiffness per MN decreased significantly with a simultaneous increase in compressed MNs. The mean buckling load and stiffness of 52 MNs in single-needle compression tests were 0.211 ± 0.008 N and 13.9 ± 1.3 N/mm, respectively, with no variation among the three MNAs. However, a significant difference in buckling load and stiffness was observed among the MNs within the MNAs. Additionally, buckling loads and stiffnesses were significantly lower in certain MNs at the same location in different MNAs. Buckling load and stiffness decreased significantly during inclined compression compared to during vertical compression. While the tests evaluate the mechanical properties of MNAs, test results may vary depending on test conditions. Conclusions: Compression testing of the individual MNs comprising an MNA helps evaluate the mechanical properties of MNs and ensure the quality of MNAs. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
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14 pages, 2945 KiB  
Article
Application of the Thermal Analysis of Frozen Aqueous Solutions to Assess the Miscibility of Hyaluronic Acid and Polymers Used for Dissolving Microneedles
by Ken-ichi Izutsu, Hiroyuki Yoshida, Yasuhiro Abe, Eiichi Yamamoto, Yoji Sato and Daisuke Ando
Pharmaceutics 2024, 16(10), 1280; https://doi.org/10.3390/pharmaceutics16101280 - 30 Sep 2024
Viewed by 856
Abstract
Background: The combination of multiple polymers is anticipated to serve as a means to diversify the physical properties and functionalities of dissolving microneedles. The mixing state of components is considered as a crucial factor in determining their suitability. Objectives: The purpose of this [...] Read more.
Background: The combination of multiple polymers is anticipated to serve as a means to diversify the physical properties and functionalities of dissolving microneedles. The mixing state of components is considered as a crucial factor in determining their suitability. Objectives: The purpose of this study was to elucidate whether thermal analysis of frozen aqueous solutions can appropriately predict the miscibility of hyaluronic acid (HA) and other polymers used for dissolving microneedles prepared by a micromolding method. Methods: Aliquots of aqueous polymer solutions were applied for thermal analysis by heating the samples from −70 °C at 5 °C/min to obtain the transition temperature of amorphous polymers and/or the crystallization/melting peaks of polymers (e.g., polyethylene glycol (PEG)). Films and dissolving microneedles were prepared by air-drying of the aqueous polymer solutions to assess the polymer miscibility in the solids. Results: The frozen aqueous single-solute HA solutions exhibited a clear Tg′ (the glass transition temperature of maximally freeze-concentrated solutes) at approximately −20 °C. The combination of HA with several polymers (e.g., dextran FP40, DEAE-dextran, dextran sulfate, and gelatin) showed a single Tg′ transition at temperatures that shifted according to their mass ratio, which strongly suggested the mixing of the freeze-concentrated solutes. By contrast, the observation of two Tg′ transitions in a scan strongly suggested the separation of HA and polyvinylpyrrolidone (PVP) or HA and polyacrylic acid (PAA) into different freeze-concentrated phases, each of which was rich in an amorphous polymer. The combination of HA and PEG exhibited the individual physical changes of the polymers. The polymer combinations that showed phase separation in the frozen solution formed opaque films and microneedles upon their preparation by air-drying. Coacervation occurring in certain polymer combinations was also suggested as a factor contributing to the formation of cloudy films. Conclusions: Freezing aqueous polymer solutions creates a highly concentrated polymer environment that mimics the matrix of dissolving microneedles prepared through air drying. This study demonstrated that thermal analysis of the frozen solution offers insights into the mixing state of condensed polymers, which can be useful for predicting the physical properties of microneedles. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
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13 pages, 1513 KiB  
Article
Development of Norelgestromin Dissolving Bilayer Microarray Patches for Sustained Release of Hormonal Contraceptive
by Lalitkumar K. Vora, Ismaiel A. Tekko, Fabiana Volpe Zanutto, Akmal Sabri, Robert K. M. Choy, Jessica Mistilis, Priscilla Kwarteng, Maggie Kilbourne-Brook, Courtney Jarrahian, Helen O. McCarthy and Ryan F. Donnelly
Pharmaceutics 2024, 16(7), 946; https://doi.org/10.3390/pharmaceutics16070946 - 17 Jul 2024
Cited by 2 | Viewed by 3471
Abstract
Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards [...] Read more.
Microarray patches (MAPs) offer a noninvasive and patient-friendly drug delivery method, suitable for self-administration, which is especially promising for low- and middle-income country settings. This study focuses on the development of dissolving bilayer MAPs loaded with norelgestromin (NGMN) as a first step towards developing a future potential drug delivery system for sustained hormonal contraception. The fabricated MAPs were designed with the appropriate needle lengths to penetrate the stratum corneum, while remaining minimally stimulating to dermal nociceptors. Ex vivo assessments showed that the MAPs delivered an average of 176 ± 60.9 μg of NGMN per MAP into excised neonatal porcine skin, representing 15.3 ± 5.3% of the loaded drug. In vivo pharmacokinetic analysis in Sprague Dawley rats demonstrated a Tmax of 4 h and a Cmax of 67.4 ± 20.1 ng/mL for the MAP-treated group, compared to a Tmax of 1 h and a Cmax of 700 ± 138 ng/mL for the intramuscular (IM) injection group, with a relative bioavailability of approximately 10% for the MAPs. The MAP-treated rats maintained plasma levels sufficient for therapeutic effects for up to 7 days after a single application. These results indicate the potential of NGMN-loaded dissolving bilayer MAPs, with further development focused on extending the release duration and improving bioavailability for prolonged contraceptive effects. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
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31 pages, 7459 KiB  
Article
Polymeric Microneedles Enhance Transdermal Delivery of Therapeutics
by Hiep X. Nguyen, Thomas Kipping and Ajay K. Banga
Pharmaceutics 2024, 16(7), 845; https://doi.org/10.3390/pharmaceutics16070845 - 22 Jun 2024
Cited by 2 | Viewed by 2210
Abstract
This research presents the efficacy of polymeric microneedles in improving the transdermal permeation of methotrexate across human skin. These microneedles were fabricated from PLGA Expansorb® 50-2A and 50-8A and subjected to comprehensive characterization via scanning electron microscopy, Fourier-transform infrared spectroscopy, and mechanical [...] Read more.
This research presents the efficacy of polymeric microneedles in improving the transdermal permeation of methotrexate across human skin. These microneedles were fabricated from PLGA Expansorb® 50-2A and 50-8A and subjected to comprehensive characterization via scanning electron microscopy, Fourier-transform infrared spectroscopy, and mechanical analysis. We developed and assessed a methotrexate hydrogel for physicochemical and rheological properties. Dye binding, histological examinations, and assessments of skin integrity demonstrated the effective microporation of the skin by PLGA microneedles. We measured the dimensions of microchannels in the skin using scanning electron microscopy, pore uniformity analysis, and confocal microscopy. The skin permeation and disposition of methotrexate were researched in vitro. PLGA 50-8A microneedles appeared significantly longer, sharper, and more mechanically uniform than PLGA 50-2A needles. PLGA 50-8A needles generated substantially more microchannels, as well as deeper, larger, and more uniform channels in the skin than PLGA 50-2A needles. Microneedle insertion substantially reduced skin electrical resistance, accompanied by an elevation in transepidermal water loss values. PLGA 50-8A microneedle treatment provided a significantly higher cumulative delivery, flux, diffusion coefficient, permeability coefficient, and predicted steady-state plasma concentration; however, there was a shorter lag time than for PLGA 50-2A needles, base-treated, and untreated groups (p < 0.05). Conclusively, skin microporation using polymeric microneedles significantly improved the transdermal delivery of methotrexate. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
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Review

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53 pages, 5785 KiB  
Review
Revolutionizing Eye Care: Exploring the Potential of Microneedle Drug Delivery
by Satish Rojekar, Swapnali Parit, Amol D. Gholap, Ajit Manchare, Sopan N. Nangare, Navnath Hatvate, Vrashabh V. Sugandhi, Keshav Raj Paudel and Rahul G. Ingle
Pharmaceutics 2024, 16(11), 1398; https://doi.org/10.3390/pharmaceutics16111398 - 30 Oct 2024
Viewed by 1781
Abstract
Microneedle technology revolutionizes ocular drug delivery by addressing challenges in treating ocular diseases. This review explores its potential impact, recent advancements, and clinical uses. This minimally invasive technique offers precise control of drug delivery to the eye, with various microneedle types showing the [...] Read more.
Microneedle technology revolutionizes ocular drug delivery by addressing challenges in treating ocular diseases. This review explores its potential impact, recent advancements, and clinical uses. This minimally invasive technique offers precise control of drug delivery to the eye, with various microneedle types showing the potential to penetrate barriers in the cornea and sclera, ensuring effective drug delivery. Recent advancements have improved safety and efficacy, offering sustained and controlled drug delivery for conditions like age-related macular degeneration and glaucoma. While promising, challenges such as regulatory barriers and long-term biocompatibility persist. Overcoming these through interdisciplinary research is crucial. Ultimately, microneedle drug delivery presents a revolutionary method with the potential to significantly enhance ocular disease treatment, marking a new era in eye care. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
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17 pages, 1788 KiB  
Review
Microneedle-Mediated Transdermal Delivery of Genetic Materials, Stem Cells, and Secretome: An Update and Progression
by Avelia Devina Calista Nainggolan, Qonita Kurnia Anjani, Pietradewi Hartrianti, Ryan F. Donnelly, Arief Kurniawan and Delly Ramadon
Pharmaceutics 2023, 15(12), 2767; https://doi.org/10.3390/pharmaceutics15122767 - 13 Dec 2023
Cited by 3 | Viewed by 2734
Abstract
Medical practitioners commonly use oral and parenteral dosage forms to administer drugs to patients. However, these forms have certain drawbacks, particularly concerning patients’ comfort and compliance. Transdermal drug delivery presents a promising solution to address these issues. Nevertheless, the stratum corneum, as [...] Read more.
Medical practitioners commonly use oral and parenteral dosage forms to administer drugs to patients. However, these forms have certain drawbacks, particularly concerning patients’ comfort and compliance. Transdermal drug delivery presents a promising solution to address these issues. Nevertheless, the stratum corneum, as the outermost skin layer, can impede drug permeation, especially for macromolecules, genetic materials, stem cells, and secretome. Microneedles, a dosage form for transdermal delivery, offer an alternative approach, particularly for biopharmaceutical products. In this review, the authors will examine the latest research on microneedle formulations designed to deliver genetic materials, stem cells, and their derivatives. Numerous studies have explored different types of microneedles and evaluated their ability to deliver these products using preclinical models. Some of these investigations have compared microneedles with conventional dosage forms, demonstrating their significant potential for advancing the development of biotherapeutics in the future. Full article
(This article belongs to the Special Issue Microarray Patches for Transdermal Drug Delivery)
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