Microneedles for intradermal and transdermal drug delivery

Abstract

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum, impose significant limitations for successful systemic delivery of broad range of therapeutic molecules particularly macromolecules and genetic material. Microneedle (MN) has been proposed as a strategy to breach the stratum corneum barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves use of micron sized needles fabricated of different materials and geometries to create transient aqueous conduits across the skin. MN, alone or with other enhancing strategies, has been demonstrated to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo experiments. This suggested the promising use of MN technology for various possible clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. MN has been proved as minimally invasive and painless in human subjects. This review article focuses on recent and future developments for MN technology including the latest type of MN design, challenges and strategies in MNs development as well as potential safety aspects based on comprehensive literature review pertaining to MN studies to date.

Keywords: Drug monitoring; Hydrogel-forming; Microneedle; Safety; Transdermal drug delivery; Vaccination.

Figure 1. Various strategies for enhancing the delivery of macromolecules across the skin.

Figure 2. Schematic representation of the mechanism of action of a microneedle array device.

The device perforates the stratum corneum (SC) providing direct access of drugs to the underlying viable epidermis, without reaching blood vessels and nerve fibres located in the dermis.

Figure 3. A schematic representation of four different MN application methods used to facilitate drug delivery transdermally.

(a) Solid MNs for increasing the permeability of a drug formulation by creating micro-holes across the skin. (b) Coated MNs for rapid dissolution of the coated drug into the skin. (c) Dissolvable MNs for rapid or controlled release of the drug incorporated within the microneedles. (d) Hollow MNs used to puncture the skin and enable release of a liquid drug following active infusion or diffusion of the formulation through the needle bores. This image was reproduced with the kind permission of Donnelly et al. (2012).

Figure 4. Novel hydrogel-forming MNs facilitate controlled transdermal drug delivery.

(a) An expanded view of the backing layer, drug-loaded adhesive patch and solid crosslinked hydrogel MN array which constitutes an integrated hydrogel MN patch. (b) Application of the integrated hydrogel MN patch to the skin surface. (c) Diffusion of water into the MN array leading to controlled swelling of the arrays and diffusion of drug molecules from the adhesive patch through the hydrogel conduit. (d) Intact hydrogel MN arrays following removal from the skin. This image was reproduced with kind permission from Donnelly et al. (2012).