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Pharmaceutics
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Microneedle Patches: Developing Strategies for Delivery
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Microneedle Patches: Developing Strategies for Delivery

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

Deadline for manuscript submissions: closed (31 August 2015) | Viewed by 118486

Special Issue Editors

Dr. Diganta Bhusan Das

E-Mail Website
Guest Editor
Department of Chemical Engineering, School of Aeronautical, Automotive, Chemical and Materials Engineering (AACME), Loughborough University, Loughborough LE11 3TU, UK
Interests: water and soil security; wastewater treatment
Special Issues, Collections and Topics in MDPI journals
Dr. Ololade Olatunji

E-Mail Website
Guest Editor
Chemical Engineering Department, Faculty of Engineering, University of Lagos Akoka, Lagos, Nigeria

Special Issue Information

Dear Colleagues,

Microneedle technology for drug delivery has grown significantly in the last 15 years. Microneedles have been shown to be able to deliver a range of drugs, vaccines, and genes, e.g., large molecular weight drugs that are larger than 500 Da. Microneedles are very versatile in delivering either solid or liquid drug formulations. Furthermore, it has been shown that microneedle technology can be combined with other methods, such as ultrasound and iontophoresis. Microneedles have been manufactured from a wide range of materials, such as polymers (e.g., polycarbonates and silk fibroin) and metals (e.g., titanium and stainless steel). Novel techniques of production have also been introduced in the past few decades, which include spatially discrete thermal drawing, centrifuge molding, and laser drilling. Microneedles have a promising prospect to transform drug and vaccine delivery, with the potential to improve mass vaccination programs, and facilitate more controlled drug delivery to delicate areas, such as the eye and neurons, thus eliminating the pain, discomfort, and risks associated with drug delivery via hypodermic needles. In particular, there is a significant amount of interest in the area of insulin delivery, where use of microneedles results in a drug release profile, which better mimics the natural insulin release in the body. The prospect of dose sparing and improved stability of vaccines in the dry form has raised a lot of research interest in vaccine delivery via microneedles. Thus, microneedle technology is an increasingly broad area of research interest. Keeping these facts in mind, the journal Special Issue invites papers on the following areas:

(i) Materials for microneedle systems

(ii) Manufacture of microneedle systems

(iii)Combination of microneedles with other methods

(iv) Pre-clinical and clinical studies using microneedle systems

(v) Modeling and optimization of microneedle systems

(vi) Permeation studies involving microneedle pierced skin.

Dr. Diganta B Das
Dr. Ololade Olatunji
Guest Editor

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Keywords

  • microneedle
  • permeation study
  • modeling and optimization
  • materials for microneedles
  • manufacturing method

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Published Papers (8 papers)

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Research

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3762 KiB  
Article
Insertion Process of Ceramic Nanoporous Microneedles by Means of a Novel Mechanical Applicator Design
by Xavier H. M. Hartmann, Peter Van der Linde, Erik F. G. A. Homburg, Lambert C. A. Van Breemen, Arthur M. De Jong and Regina Luttge
Pharmaceutics 2015, 7(4), 503-522; https://doi.org/10.3390/pharmaceutics7040503 - 18 Nov 2015
Cited by 22 | Viewed by 7001
Abstract
Arrays of microneedles (MNAs) are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft-lithography and micromolding to manufacture ceramic nanoporous (np)MNAs. Failure modes of ceramic npMNAs are as [...] Read more.
Arrays of microneedles (MNAs) are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft-lithography and micromolding to manufacture ceramic nanoporous (np)MNAs. Failure modes of ceramic npMNAs are as yet poorly understood and the question remained: is our npMNA platform technology ready for microneedle (MN) assembly into patches? We investigated npMNAs by microindentation, yielding average crack fracture forces above the required insertion force for a single MN to penetrate human skin. We further developed a thumb pressure-actuated applicator-assisted npMNA insertion method, which enables anchoring of MNs in the skin by an adhesive in one handling step. Using a set of simple artificial skin models, we found a puncture efficiency of this insertion method a factor three times higher than by applying thumb pressure on the npMNA base plate directly. In addition, this new method facilitated zero MN-breakage due to a well-defined force distribution exerted onto the MNs and the closely surrounding area prior to bringing the adhesive into contact with the skin. Owing to the fact that such parameter space exists, we can conclude that npMNAs by soft lithography are a platform technology for MN assembly into a patch. Full article
(This article belongs to the Special Issue Microneedle Patches: Developing Strategies for Delivery)
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3040 KiB  
Article
Investigation of Plasma Treatment on Micro-Injection Moulded Microneedle for Drug Delivery
by Karthik Nair, Benjamin Whiteside, Colin Grant, Rajnikant Patel, Cristina Tuinea-Bobe, Keith Norris and Anant Paradkar
Pharmaceutics 2015, 7(4), 471-485; https://doi.org/10.3390/pharmaceutics7040471 - 30 Oct 2015
Cited by 39 | Viewed by 9383
Abstract
Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy [...] Read more.
Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA. Full article
(This article belongs to the Special Issue Microneedle Patches: Developing Strategies for Delivery)
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2555 KiB  
Article
Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic Antimicrobial Chemotherapy of Infected Wounds
by Ester Caffarel-Salvador, Mary-Carmel Kearney, Rachel Mairs, Luigi Gallo, Sarah A. Stewart, Aaron J. Brady and Ryan F. Donnelly
Pharmaceutics 2015, 7(4), 397-412; https://doi.org/10.3390/pharmaceutics7040397 - 28 Sep 2015
Cited by 60 | Viewed by 8702
Abstract
Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has [...] Read more.
Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has been termed “photodynamic antimicrobial chemotherapy” (PACT). In the treatment of chronic wounds, the delivery of photosensitising agents is often impeded by the presence of a thick hyperkeratotic/necrotic tissue layer, reducing their therapeutic efficacy. Microneedles (MNs) are an emerging drug delivery technology that have been demonstrated to successfully penetrate the outer layers of the skin, whilst minimising damage to skin barrier function. Delivering photosensitising drugs using this platform has been demonstrated to have several advantages over conventional photodynamic therapy, such as, painless application, reduced erythema, enhanced cosmetic results and improved intradermal delivery. The aim of this study was to physically characterise dissolving MNs loaded with the photosensitising agent, methylene blue and assess their photodynamic antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of Gantrez® AN-139 co-polymer containing varying loadings of methylene blue. A height reduction of 29.8% was observed for MNs prepared from blends containing 0.5% w/w methylene blue following application of a total force of 70.56 N/array. A previously validated insertion test was used to assess the effect of drug loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia coli and Candida albicans biofilms were incubated with various methylene blue concentrations within the range delivered by MNs in vitro (0.1–2.5 mg/mL) and either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period. Microbial susceptibility to PACT was determined by assessing the total viable count. Kill rates of >96%, were achieved for S. aureus and >99% for E. coli and C. albicans with the combination of PACT and methylene blue concentrations between 0.1 and 2.5 mg/mL. A reduction in the colony count was also observed when incorporating the photosensitiser without irradiation, this reduction was more notable in S. aureus and E. coli strains than in C. albicans. Full article
(This article belongs to the Special Issue Microneedle Patches: Developing Strategies for Delivery)
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1103 KiB  
Article
Solid Microneedles for Transdermal Delivery of Amantadine Hydrochloride and Pramipexole Dihydrochloride
by Mylien T. Hoang, Kevin B. Ita and Daniel A. Bair
Pharmaceutics 2015, 7(4), 379-396; https://doi.org/10.3390/pharmaceutics7040379 - 28 Sep 2015
Cited by 66 | Viewed by 9408
Abstract
The aim of this project was to study the influence of microneedles on transdermal delivery of amantadine hydrochloride and pramipexole dihydrochloride across porcine ear skin in vitro. Microchannel visualization studies were carried out and characterization of the microchannel depth was performed using [...] Read more.
The aim of this project was to study the influence of microneedles on transdermal delivery of amantadine hydrochloride and pramipexole dihydrochloride across porcine ear skin in vitro. Microchannel visualization studies were carried out and characterization of the microchannel depth was performed using confocal laser scanning microscopy (CLSM) to demonstrate microchannel formation following microneedle roller application. We also report, for the first time, the use of TA.XT Plus Texture Analyzer to characterize burst force in pig skin for transdermal drug delivery experiments. This is the force required to rupture pig skin. The mean passive flux of amantadine hydrochloride, determined using a developed LC–MS/MS technique, was 22.38 ± 4.73 µg/cm2/h, while the mean flux following the use of a stainless steel microneedle roller was 49.04 ± 19.77 µg/cm2/h. The mean passive flux of pramipexole dihydrochloride was 134.83 ± 13.66 µg/cm2/h, while the flux following the use of a stainless steel microneedle roller was 134.04 ± 0.98 µg/cm2/h. For both drugs, the difference in flux values following the use of solid stainless steel microneedle roller was not statistically significantly (p > 0.05). Statistical analysis was carried out using the Mann–Whitney Rank sum test. Full article
(This article belongs to the Special Issue Microneedle Patches: Developing Strategies for Delivery)
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1894 KiB  
Article
Microneedles from Fishscale-Nanocellulose Blends Using Low Temperature Mechanical Press Method
by Ololade Olatunji and Richard T. Olsson
Pharmaceutics 2015, 7(4), 363-378; https://doi.org/10.3390/pharmaceutics7040363 - 24 Sep 2015
Cited by 19 | Viewed by 6969
Abstract
Fish scale biopolymer blended with nanocellulose crystals is used for production of microneedles applying mechanical press microfabrication and the effect of nanocellulose on microfabrication, water absorption, moisture stability and mechanical properties of the microneedles is reported. The results show that microneedles produced from [...] Read more.
Fish scale biopolymer blended with nanocellulose crystals is used for production of microneedles applying mechanical press microfabrication and the effect of nanocellulose on microfabrication, water absorption, moisture stability and mechanical properties of the microneedles is reported. The results show that microneedles produced from the nanocellulose loaded fish scale biopolymer requires higher temperature for micromolding (80 ± 5 °C) than microneedles from only fish scale biopolymer, which were moldable at 50 ± 5 °C. The mechanical properties of the fish scale biopolymer-nanocellulose (FSBP-NC) films showed that the addition of nanocellulose (NC) resulted in lower elongation and higher tensile stress compared to fish scale biopolymer (FSBP) films. The nanocellulose also prevented dissolution of the needles and absorbed up to 300% and 234% its own weight in water (8% and 12% w/w NC/FSBP), whereas FSBP films dissolved completely within 1 min, Indicating that the FSBP-NC films can be used to produce microneedles with prolonged dissolution rate. FTIR spectrometry of the FSBP films was compared with the FSBP-NC films and the NC gels. The FTIR showed typical peaks for fish scale polymer and nanocellulose with evidence of interactions. SEM micrographs showed relatively good dispersion of NC in FSBP at both NC contents corresponding to 8% and 12% w/w NC/FSBP respectively. Full article
(This article belongs to the Special Issue Microneedle Patches: Developing Strategies for Delivery)
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Review

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965 KiB  
Review
Microneedle Coating Techniques for Transdermal Drug Delivery
by Rita Haj-Ahmad, Hashim Khan, Muhammad Sohail Arshad, Manoochehr Rasekh, Amjad Hussain, Susannah Walsh, Xiang Li, Ming-Wei Chang and Zeeshan Ahmad
Pharmaceutics 2015, 7(4), 486-502; https://doi.org/10.3390/pharmaceutics7040486 - 5 Nov 2015
Cited by 119 | Viewed by 14027
Abstract
Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a [...] Read more.
Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates. Full article
(This article belongs to the Special Issue Microneedle Patches: Developing Strategies for Delivery)
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3307 KiB  
Review
Transdermal Drug Delivery: Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of the Stratum Corneum
by Ahlam Zaid Alkilani, Maelíosa T. C. McCrudden and Ryan F. Donnelly
Pharmaceutics 2015, 7(4), 438-470; https://doi.org/10.3390/pharmaceutics7040438 - 22 Oct 2015
Cited by 771 | Viewed by 37586
Abstract
The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner [...] Read more.
The skin offers an accessible and convenient site for the administration of medications. To this end, the field of transdermal drug delivery, aimed at developing safe and efficacious means of delivering medications across the skin, has in the past and continues to garner much time and investment with the continuous advancement of new and innovative approaches. This review details the progress and current status of the transdermal drug delivery field and describes numerous pharmaceutical developments which have been employed to overcome limitations associated with skin delivery systems. Advantages and disadvantages of the various approaches are detailed, commercially marketed products are highlighted and particular attention is paid to the emerging field of microneedle technologies. Full article
(This article belongs to the Special Issue Microneedle Patches: Developing Strategies for Delivery)
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1096 KiB  
Review
Transdermal Delivery of Drugs with Microneedles—Potential and Challenges
by Kevin Ita
Pharmaceutics 2015, 7(3), 90-105; https://doi.org/10.3390/pharmaceutics7030090 - 29 Jun 2015
Cited by 370 | Viewed by 22477
Abstract
Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be [...] Read more.
Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use. Full article
(This article belongs to the Special Issue Microneedle Patches: Developing Strategies for Delivery)
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