Optimisation of microneedle array design for microneedle mediated iontophoretic transdermal drug delivery
In order to exploit the transdermal route for systemic delivery of a wide range of drug molecules, including peptide/protein molecules, a means of overcoming the excellent barrier properties of the uppermost layer of the skin, the stratum corneum must be sought. It has recently been suggested that a combination of microneedle (MN) and iontophoresis (ITP) technologies may broaden the range of macromolecules that may be successfully delivered across the skin, with the added benefit of precise electronic control over the rate of transdermal drug delivery. MNs are micron scale devices, up to 1.5 mm in length, that physically disrupt the stratum corneum and thus may be used to create aqueous pathways for the electrically facilitated transport of a variety of molecules across the skin. The present study was designed to identify the most suitable polymeric MN array design for use as an electrically responsive device capable of providing both sustained and on-demand percutaneous drug delivery both in vitro and in vivo. Soluble MN arrays loaded with a range of small to large molecules were fabricated from aqueous blends of 20% w/w poly(methyl vinyl ether co maleic acid) (PMVE/MA). Novel hydrogel forming MN arrays were fabricated from aqueous blends containing 15% w/w PMVEIMA and 7.5% w/w poly(ethyleneglycol) (PEG, Mw = 10 kDa). MN arrays were fabricated in a laser-engineered micro-moulding process. Hydrogel MN arrays were integrated with drug loaded reservoir patches. Whilst the combination of ITP with both polymeric MN systems led to enhanced transdermal delivery of all drug molecules investigated in vitro, the electro-responsive nature of the hydrogel forming MN arrays enabled the sustained passive delivery and the electrically stimulated bolus delivery of the proteins insulin and bovine serum albumin in vivo. As such, this system may have great potential for the pulsatile transdermal delivery of therapeutic peptide/protein agents.
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