Influence of molecular weight on transdermal delivery of model macromolecules using hydrogel-forming microneedles: potential to enhance the administration of novel low molecular weight biotherapeutics

Hutton, Aaron R.J.; McCrudden, Maeliosa; Larrañeta, Eneko; Donnelly, Ryan F.

doi:10.1039/d0tb00021c

Cited by 32 publications

(24 citation statements)

References 37 publications

(45 reference statements)

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“…In TDDS, it is generally accepted that the delivery of substances with small molecular weights utilizes the intracellular pathway. However, for substances having a large molecular weight, methods and various mechanisms using the intracellular pathway in addition to the intercellular pathway are introduced and used [ 15 – 17 ]. This is due to the structure of the skin because the part called lipid containing both cells and hydrophilic substances and hydrophobic substances does not have a perfectly regular position but exists with regularity [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Recent advances in transdermal drug delivery systems: a review

et al. 2021

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Various non-invasive administrations have recently emerged as an alternative to conventional needle injections. A transdermal drug delivery system (TDDS) represents the most attractive method among these because of its low rejection rate, excellent ease of administration, and superb convenience and persistence among patients. TDDS could be applicable in not only pharmaceuticals but also in the skin care industry, including cosmetics. Because this method mainly involves local administration, it can prevent local buildup in drug concentration and nonspecific delivery to tissues not targeted by the drug. However, the physicochemical properties of the skin translate to multiple obstacles and restrictions in transdermal delivery, with numerous investigations conducted to overcome these bottlenecks. In this review, we describe the different types of available TDDS methods, along with a critical discussion of the specific advantages and disadvantages, characterization methods, and potential of each method. Progress in research on these alternative methods has established the high efficiency inherent to TDDS, which is expected to find applications in a wide range of fields.

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Section: Introductionmentioning

confidence: 99%

Recent advances in transdermal drug delivery systems: a review

et al. 2021

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“…FITC-dextran (10 kDa) and fluorescein sodium–loaded lyophilised wafers were prepared using 10% w/w gelatin and 5% w/w mannitol as detailed by Hutton et al [ 21 ]. Briefly, the fluorescent compound was first dissolved in deionised water and heated to 37 °C.…”

Section: Methodsmentioning

confidence: 99%

“…The addition of Na 2 CO 3 results in the formation of sodium salts on free carboxylic acid groups, generating a more porous structure and increasing the degree of swelling. Therefore, the lower density and greater space within the polymer itself permits greater permeation of higher MW macromolecules such as FITC-dextran 10 kDa examined in this study [ 21 ]. By designing an alternative method to improve the applicability of hydrogel-forming MAPs, this unique study could have important implications for future patient acceptance.…”

Section: Introductionmentioning

confidence: 99%

Designing a unique feedback mechanism for hydrogel-forming microneedle array patches: a concept study

Hutton

Kirkby

Larrañeta

et al. 2021

Drug Deliv. and Transl. Res.

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Although microneedle array patch (MAP) technology is reaching ever closer to regulatory approval, it remains imperative that approaches to further improve patient acceptance are still explored. Addressing this perception, a water-filled reservoir was incorporated into a hydrogel-forming MAP system to provide a novel feedback mechanism. To confirm successful MAP skin insertion, the end user would both hear and feel the rupture of the water-filled reservoir. Interestingly, a 50-µL water-filled reservoir ruptured at 30.27 ± 0.39 N, which has previously been shown as the mean application force for MN insertion in human subjects following appropriate instruction. Importantly, no significant difference in % cumulative permeation of FITC-dextran 10 kDa and fluorescein sodium after 24 h was observed between a 50-µL reservoir and the current method of application that has been successfully used in both in vitro and in vivo studies (p > 0.05). Therefore, as drug delivery was not affected, this proof-of-concept study has shown that a water-filled reservoir feedback mechanism has the potential to serve as a viable tool for consistent MAP skin insertion. Graphical abstract

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“…Thus, pain or bleeding do not occur. Increasing evidence is displayed in the literature of the great promise of MAPs to enhance the transdermal delivery of both low-and high-molecular-weight therapeutic agents [5][6][7][8][9][10][11][12][13][14]. Research has focused on different types of MAPs made from a wide range of materials.…”

Section: Introductionmentioning

confidence: 99%

Novel Design Approaches in the Fabrication of Polymeric Microarray Patches via Micromoulding

et al. 2020

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The focus on novel systems for transdermal delivery of therapeutic agents has increased considerably over recent years, as this administration route comes with many advantages. Polymeric microarray patches (MAPs) are minimally invasive devices that enable systemic delivery of a wide range of drugs by overcoming the outer skin barrier. Conventionally, MAPs fabricated by micromoulding have a low needle density. In this study, the performance of hydrogel-forming MAPs cast using novel industrially manufactured micromoulds with a high needle density (600 needles/0.75 cm2) was compared to that of MAPs obtained using conventional moulds with a lower density (196 needles/0.89 cm2). Surrounding holders for micromoulds were designed for time-efficient fabrication of MAPs. The influence of needle densities on mechanical strength, insertion efficiency and in vitro permeation of ibuprofen sodium (IBU) was analysed. Insertion of both MAPs into an artificial skin model and neonatal porcine skin was comparable. No significant difference was observed in permeation studies of IBU (p > 0.05), with a delivery of 8.7 ± 1.7 mg for low-density and 9.5 ± 0.1 mg for high-density MAPs within 24 h. This highlights the potential of these novel micromoulds for manufacturing polymeric MAPs with a higher needle density for future applications.

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Influence of molecular weight on transdermal delivery of model macromolecules using hydrogel-forming microneedles: potential to enhance the administration of novel low molecular weight biotherapeutics

Abstract: For the first time, we have shown that molecular weight plays a role in permeation through a ‘super-swelling’ microneedle system.

Cited by 32 publications

References 37 publications

Recent advances in transdermal drug delivery systems: a review

Recent advances in transdermal drug delivery systems: a review

Designing a unique feedback mechanism for hydrogel-forming microneedle array patches: a concept study

Novel Design Approaches in the Fabrication of Polymeric Microarray Patches via Micromoulding

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