Drug Delivery Systems Using Various Microneedle Technologies

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 37283

Special Issue Editor

Department of Chemical & Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
Interests: microneedles; biomedical device; drug delivery; gene therapy; vaccine research; smart biopolymer; cell-penetrating peptide

Special Issue Information

Dear Colleagues,

Microneedles are an array of micron-scale needles that are capable of penetrating the outermost layer of skin, the stratum corneum, for efficient transdermal delivery. Because transdermal delivery has potential advantages over other routes of administration, it is a highly recommended route for drug delivery. Therefore, research on microneedle technology has been attracting huge attention not only from the scientific world but also from general personals for the past two decades. Conventional hypodermic needle injections have been replaced with various types of microneedles because of their unique mechanical strength, shape and delivery mechanisms for different types of biomolecules. The microneedles has dramatically grown over the past couple of years and new fabrication technologies have enabled a nimiety of microneedles for drug delivery across the skin and other organs.

We would encourage scientists from microneedles areas to contribute original and review articles regarding the recent advances in drug delivery systems using various microneedle technologies.

Prof. Dr. Yeu-Chun Kim
Guest Editor

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Keywords

  • Transdermal drug delivery
  • Microneedles
  • Skin vaccination

Published Papers (7 papers)

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Research

12 pages, 2211 KiB  
Article
Micro-Pillar Integrated Dissolving Microneedles for Enhanced Transdermal Drug Delivery
by Seunghee Lee, Shayan Fakhraei Lahiji, Jeesu Jang, Mingyu Jang and Hyungil Jung
Pharmaceutics 2019, 11(8), 402; https://doi.org/10.3390/pharmaceutics11080402 - 10 Aug 2019
Cited by 31 | Viewed by 5397
Abstract
The dissolving microneedle (DMN) patch is a transdermal delivery system, containing arrays of micro-sized polymeric needles capable of encapsulating therapeutic drugs within their matrix and releasing them into the skin. However, the elastic properties of the skin prevent DMNs from complete insertion and [...] Read more.
The dissolving microneedle (DMN) patch is a transdermal delivery system, containing arrays of micro-sized polymeric needles capable of encapsulating therapeutic drugs within their matrix and releasing them into the skin. However, the elastic properties of the skin prevent DMNs from complete insertion and accurate delivery of encapsulated compounds into the skin. Moreover, the adhesive materials used in patches may cause skin irritation, inflammation, and redness. Therefore, we developed a patchless, micro-pillar integrated DMN (P-DMN) that is simple to fabricate and enhances transdermal drug delivery compared with traditional DMN patches. The micro-pillars were made of polymethyl methacrylate at a height of 300 μm and a base diameter of 500 μm. To fabricate P-DMNs, we employed hyaluronic acid, which is a widely used derma filler and plays a role in tissue re-epithelialization. We demonstrate that utilizing P-DMNs significantly improves the delivery efficiency of an encapsulated drug surrogate (91.83% ± 7.75%) compared with traditional DMNs (64.86% ± 8.17%). Interestingly, P-DMNs remarkably increase the skin penetration accuracy rate of encapsulated drugs, up to 97.78% ± 2.22%, compared with 44.44% ± 7.85% in traditional DMNs. Our findings suggest that P-DMNs could serve as a highly accurate and efficient platform for transdermal delivery of various types of micro- and macro-biomolecules. Full article
(This article belongs to the Special Issue Drug Delivery Systems Using Various Microneedle Technologies)
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22 pages, 6021 KiB  
Article
Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study
by Andi Dian Permana, Maelíosa T. C. McCrudden and Ryan F. Donnelly
Pharmaceutics 2019, 11(7), 346; https://doi.org/10.3390/pharmaceutics11070346 - 17 Jul 2019
Cited by 72 | Viewed by 5918
Abstract
Conventional oral administration of antifilariasis drugs results in nonspecific targeting of the drugs and the intradermal delivery of nanoparticles with sizes of <100 nm could be used to improve lymphatic uptake. This study investigated the combination of nanosuspension and dissolving microneedles (MN-NS) as [...] Read more.
Conventional oral administration of antifilariasis drugs results in nonspecific targeting of the drugs and the intradermal delivery of nanoparticles with sizes of <100 nm could be used to improve lymphatic uptake. This study investigated the combination of nanosuspension and dissolving microneedles (MN-NS) as an alternative intradermal delivery approach for the delivery of antifilariasis drugs, namely doxycycline, albendazole, and ivermectin. NS were fabricated and optimized using a bottom-up technique. The NS were then incorporated into the MN arrays. The optimized NS were <100 nm in diameter. Furthermore, MN-NS had suitable mechanical strength and insertion capabilities. The dermatokinetic study revealed that the delivery of drugs into the dermis of excised neonatal porcine skin by MNs was significantly higher than that from a needle-free patch, with 29.29 ± 4.65%, 31.54 ± 5.35%, and 34.54 ± 4.98% of doxycycline, albendazole sulfoxide, and ivermectin retained in the dermis after 24 h. The results presented here serve as proof of concept for the significant enhancement of drug retention times in the dermis, following their formulation into NS and delivery via MN. Leading on from these studies, future work must investigate in vivo lymphatic pharmacokinetic profiling of drugs formulated into NS, in a suitable animal model. Full article
(This article belongs to the Special Issue Drug Delivery Systems Using Various Microneedle Technologies)
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11 pages, 3514 KiB  
Article
Delivery of Niacinamide to the Skin Using Microneedle-Like Particles
by Chong In Shin, MunSik Kim and Yeu-Chun Kim
Pharmaceutics 2019, 11(7), 326; https://doi.org/10.3390/pharmaceutics11070326 - 11 Jul 2019
Cited by 9 | Viewed by 3879
Abstract
The stratum corneum is the outermost skin layer that obstructs the delivery of active ingredients found in cosmeceutical products. Chemical peels and microbeads have been used to overcome this layer, but these methods can cause side effects and are not environmentally friendly. While [...] Read more.
The stratum corneum is the outermost skin layer that obstructs the delivery of active ingredients found in cosmeceutical products. Chemical peels and microbeads have been used to overcome this layer, but these methods can cause side effects and are not environmentally friendly. While microneedles do not share the dangers mentioned above, they are currently only available as patches, which makes them unsuitable to be used with products that are usually applied onto a large area of the skin surface. Therefore, the aim of this study was to develop microneedle-like particles (MLP) whose needles would disrupt the skin during the rubbing process. A modified approach taken from conventional micromolding techniques was used to make the MLPs. The experimental results show that the fabricated structures had the required mechanical strength. Furthermore, after the application of the MLPs, the permeability of two fluorescent dyes, fluorescein sodium salt and sulforhodamine B increased to 217.6% ± 25.6% and 251.7% ± 12.8% respectively. Additionally, the permeability of a model drug, niacinamide, was shown to have increased to 193.8% ± 29.9%. Cryosectioned porcine slices also confirmed the ability of MLPs to enhance skin permeability by revealing a deeper penetration of the applied fluorescent dye. Altogether, the results demonstrate the potential of MLPs to be used as safe skin permeability enhancers that can be applied all over the skin. Full article
(This article belongs to the Special Issue Drug Delivery Systems Using Various Microneedle Technologies)
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13 pages, 2902 KiB  
Article
Nanosuspension-Based Dissolving Microneedle Arrays for Intradermal Delivery of Curcumin
by Sharif Abdelghany, Ismaiel A. Tekko, Lalitkumar Vora, Eneko Larrañeta, Andi Dian Permana and Ryan F. Donnelly
Pharmaceutics 2019, 11(7), 308; https://doi.org/10.3390/pharmaceutics11070308 - 02 Jul 2019
Cited by 90 | Viewed by 7394
Abstract
The objective of this study was to evaluate the intradermal delivery of curcumin utilising poly(vinylalcohol) (PVA)-based microneedles loaded with curcumin nanosuspension (CU-NS). Nanoprecipitation was used to formulate the CU-NS which was then incorporated into PVA microneedles arrays consisting of 11 × 11 microneedles [...] Read more.
The objective of this study was to evaluate the intradermal delivery of curcumin utilising poly(vinylalcohol) (PVA)-based microneedles loaded with curcumin nanosuspension (CU-NS). Nanoprecipitation was used to formulate the CU-NS which was then incorporated into PVA microneedles arrays consisting of 11 × 11 microneedles of conical shape, measuring 900 µm in height and with 300 µm base diameter. The nanosuspension particle size was 520 ± 40 nm, with a polydispersity of 0.27 ± 0.02 using sodium lauryl sulfate (SLS) as a stabiliser. In vitro dissolution studies in 10% w/v Tween 80 showed that the CU-NS dissolved significantly faster than unmodified curcumin powder, with 34% released from the CU-NS, compared to 16% from the curcumin powder after 48 h. The CU-NS-loaded microneedles (CU-MN) were able to withstand a compression force of 32 N for 30 s. Moreover, these microneedles were able to penetrate excised neonatal porcine skin to a depth of 500 µm, dissolved completely in the skin within 60 min. After CU-MN dissolution, the drug diffused from the application site and migrated through the skin layers down to 2300 µm, significantly more than observed with topical application of CU-NS. This suggest that the fabricated microneedles with the incorporated CU-NS could enhance the intradermal delivery of curcumin. Full article
(This article belongs to the Special Issue Drug Delivery Systems Using Various Microneedle Technologies)
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14 pages, 2534 KiB  
Article
Acid-Treated Water-Soluble Chitosan Suitable for Microneedle-Assisted Intracutaneous Drug Delivery
by Ajeesh Chandrasekharan, Young Jun Hwang, Keum-Yong Seong, Samdae Park, Sodam Kim and Seung Yun Yang
Pharmaceutics 2019, 11(5), 209; https://doi.org/10.3390/pharmaceutics11050209 - 02 May 2019
Cited by 39 | Viewed by 6241
Abstract
Chitosan has been widely used as a nature-derived polymeric biomaterial due to its high biocompatibility and abundance. However, poor solubility in aqueous solutions of neutral pH and multiple fabrication steps for the molding process limit its application to microneedle technology as a drug [...] Read more.
Chitosan has been widely used as a nature-derived polymeric biomaterial due to its high biocompatibility and abundance. However, poor solubility in aqueous solutions of neutral pH and multiple fabrication steps for the molding process limit its application to microneedle technology as a drug delivery carrier. Here, we present a facile method to prepare water-soluble chitosan and its application for sustained transdermal drug delivery. The water-soluble chitosan was prepared by acid hydrolysis using trifluoroacetic acid followed by dialysis in 0.1 M NaCl solutions. We successfully fabricated bullet-shaped microneedle (MN) arrays by the single molding process with neutral aqueous chitosan solutions (pH 6.0). The chitosan MN showed sufficient mechanical properties for skin insertion and, interestingly, exhibited slow dissolving behavior in wet conditions, possibly resulting from a physical crosslinking of chitosan chains. Chitosan MN patches loading rhodamine B, a model hydrophilic drug, showed prolonged release kinetics in the course of the dissolving process for more than 72 h and they were found to be biocompatible to use. Since the water-soluble chitosan can be used for MN fabrication in the mild conditions (neutral pH and 25 °C) required for the loading of bioactive agents such as proteins and achieve a prolonged release, this biocompatible chitosan MN would be suitable for sustained transdermal drug delivery of a diverse range of drugs. Full article
(This article belongs to the Special Issue Drug Delivery Systems Using Various Microneedle Technologies)
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16 pages, 2182 KiB  
Article
Co-Delivery of M2e Virus-Like Particles with Influenza Split Vaccine to the Skin Using Microneedles Enhances the Efficacy of Cross Protection
by Min-Chul Kim, Ki-Hye Kim, Jeong Woo Lee, Yu-Na Lee, Hyo-Jick Choi, Yu-Jin Jung, Yu-Jin Kim, Richard W. Compans, Mark R. Prausnitz and Sang-Moo Kang
Pharmaceutics 2019, 11(4), 188; https://doi.org/10.3390/pharmaceutics11040188 - 18 Apr 2019
Cited by 15 | Viewed by 4006
Abstract
It is a high priority to develop a simple and effective delivery method for a cross-protective influenza vaccine. We investigated skin immunization by microneedle (MN) patch with human influenza split vaccine and virus-like particles containing heterologous M2 extracellular (M2e) domains (M2e5x virus-like particles [...] Read more.
It is a high priority to develop a simple and effective delivery method for a cross-protective influenza vaccine. We investigated skin immunization by microneedle (MN) patch with human influenza split vaccine and virus-like particles containing heterologous M2 extracellular (M2e) domains (M2e5x virus-like particles (VLP)) as a cross-protective influenza vaccine candidate. Co-delivery of influenza split vaccine and M2e5x VLP to the skin by MN patch was found to confer effective protection against heterosubtypic influenza virus by preventing weight loss and reducing lung viral loads. Compared to intramuscular immunization, MN-based delivery of combined split vaccine and M2e5x VLPs shaped cellular immune responses toward T helper type 1 responses increasing IgG2a isotype antibodies as well as IFN-γ producing cells in mucosal and systemic sites. This study provides evidence that potential immunological and logistic benefits of M2e5x VLP with human influenza split vaccine delivered by MN patch can be used to develop an easy-to-administer cross-protective influenza vaccine. Full article
(This article belongs to the Special Issue Drug Delivery Systems Using Various Microneedle Technologies)
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13 pages, 2917 KiB  
Article
Three-Step Thermal Drawing for Rapid Prototyping of Highly Customizable Microneedles for Vascular Tissue Insertion
by KangJu Lee, Seung Hyun Park, JiYong Lee, Suho Ryu, Chulmin Joo and WonHyoung Ryu
Pharmaceutics 2019, 11(3), 100; https://doi.org/10.3390/pharmaceutics11030100 - 26 Feb 2019
Cited by 15 | Viewed by 3788
Abstract
Microneedles (MNs) have been extensively developed over the last two decades, and highly efficient drug delivery was demonstrated with their minimal invasiveness via a transdermal route. Recently, MNs have not only been applied to the skin but also to other tissues such as [...] Read more.
Microneedles (MNs) have been extensively developed over the last two decades, and highly efficient drug delivery was demonstrated with their minimal invasiveness via a transdermal route. Recently, MNs have not only been applied to the skin but also to other tissues such as blood vessels, scleral tissue, and corneal tissue. In addition, the objective of the MN application has been diversified, ranging from drug delivery to wound closure and biosensing. However, since most MN fabrication methods are expensive and time-consuming, they are inappropriate to prototype MNs for various tissues that have different and complex anatomies. Although several drawing-based techniques have been introduced for rapid MN production, they fabricated MNs with limited shapes, such as thin MNs with wide bases. In this study, we propose a three-step thermal drawing for rapid, prototyping MNs that can have a variety of shapes and can be fabricated on curved surfaces. Based on the temperature control of polymer bridge formation during thermal drawing, the body profile and aspect ratios of MNs were conveniently controlled, and the effect of temperature control on the body profile of MNs was explained. Thermally drawn MNs with different shapes were fabricated both on flat and curved surfaces, and they were characterized in terms of their mechanical properties and insertion into vascular tissue to find an optimal shape for vascular tissue insertion. Full article
(This article belongs to the Special Issue Drug Delivery Systems Using Various Microneedle Technologies)
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