Microneedle-Iontophoresis Combinations for Enhanced Transdermal Drug Delivery

It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery as well as enabling the rate of delivery to be achieved with precise electronic control. However, few reports exist on the combination of ITP with in situ drug-loaded polymeric MN delivery systems. Our in vitro permeation studies revealed that MN enhances transdermal drug delivery. The combination of dissolving MN and ITP did not further enhance the extent of delivery of the low molecular weight drug ibuprofen sodium after short application periods. However, the extent of peptide/protein delivery was significantly enhanced when ITP was used in combination with hydrogel-forming MN arrays. As such, hydrogel-forming MN arrays show promise for the electrically controlled transdermal delivery of biomacromolecules in a simple, one-step approach, though further technical developments will be necessary before patient benefit is realized.

Electrically-responsive anti-adherent hydrogels for photodynamic antimicrobial chemotherapy

The loading of the photosensitisers meso-Tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP), methylene blue (MB) and IMP with sodium dodecyl sulphate (SDS) into and release from hydrogels composed of the polyelectrolyte poly(methyl vinyl ether-co-maleic acid) crosslinked in a 2:1 ratio with PEG 10,000 were investigated as a potential rapid photodynamic antimicrobial chemotherapy (PACT) treatment for infected wounds using iontophoresis as a novel delivery method. Photosensitiser uptake was very high; (% TMP uptake; 95.53-96.72%) (% MB uptake; 90.58-93.26%) and was PMVE/MA concentration independent, whilst SDS severely limited TMP uptake (5.93-8.75%). Hydrogel hardness, compressibility and adhesiveness on the dermal surface of neonate porcine skin increased with PMVE/MA concentration and were significantly increased with SDS.

The ionic conductivities of the hydrogels increased with PMVE/MA concentration. Drug release was PMVE/MA concentration independent, except for drug release under iontophoteric conditions for MB and TMP (without SDS). In just 15 min, the mean% drug concentrations released of TMP, TMP (with SDS) and MB using an electric current ranged from 22.30 to 64.72 mu gml(-1), 6.37-4.59 mu gml(-1) and 11.73-36.57 mu gml(-1) respectively. These concentrations were in excess of those required to induce complete kill of clinical strains of meticillin-resistant Staphylococcus aureus and Burkholderia cepacia. Thus these results support our contention that the iontophoteric delivery of IMP and MB using anti-adherent, electrically-responsive, PEG-crosslinked PMVE/MA hydrogels are a potential option in the rapid PACT treatment of infected wounds. (c) 2012 Elsevier B.V. All rights reserved.

Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33mg (90%) of the drug initially loaded into the arrays was delivered over 24h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263μgml(-1) at the 24h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10cm(2) could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs.

Novel Delivery Systems for Transdermal and Intradermal Drug Delivery

This research book covers the major aspects relating to the use of novel delivery systems in enhancing both transdermal and intradermal drug delivery. It provides a review of transdermal and intradermal drug delivery, including the history of the field and the various methods employed to produce delivery systems from different materials such as device design, construction and evaluation, so as to provide a sound background to the use of novel systems in enhanced delivery applications.

Furthermore, it presents in-depth analyses of recent developments in this exponentially growing field, with a focus on microneedle arrays, needle-free injections, nanoparticulate systems and peptide-carrier-type systems. It also covers conventional physical enhancement strategies, such as tape-stripping, sonophoresis, iontophoresis, electroporation and thermal/suction/laser ablation Discussions about the penetration of the stratum corneum by the various novel strategies highlight the importance of the application method. Comprehensive and critical reviews of transdermal and intradermal delivery research using such systems focus on the outcomes of in vivoanimal and human studies. The book includes laboratory, clinical and commercial case studies featuring safety and patient acceptability studies carried out to date, and depicts a growing area for use of these novel systems is in intradermal vaccine delivery. The final chapters review recent patents in this field and describe the work ongoing in industry.