Synergistic effect of iontophoresis and soluble microneedles for transdermal delivery of methotrexate

Abstract

The aim of this study was to investigate the transdermal iontophoretic delivery of methotrexate, alone or in combination with microneedles, in-vitro and in-vivo using intracutaneous microdialysis in the hairless rat. The average depth of the microdialysis probe in the skin was found to be 0.54 mm. Methotrexate was stable in the presence of an applied electric field as determined by cyclic voltammetry. A current density of 0.4 mA cm(-2) applied for 60 min was used in combination with maltose microneedles to enhance delivery of methotrexate across the skin. Delivery was enhanced by iontophoresis and microneedles, both in-vitro and in-vivo. A synergistic 25-fold enhancement of delivery was observed in-vivo when a combination of microneedles and ionto- phoresis was used compared with either modality alone.

Characterization of Microchannels Created by Metal Microneedles: Formation and Closure

“…Several enhancement methods such as intraepidermal administration, iontophoresis, ultrasound, electroporation, chemical enhancers, and microneedles (MN) have been employed to overcome this barrier (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) and new minimally invasive techniques are continually being investigated. While chemical enhancers have been widely investigated for enhancing drug permeation levels, they tend to disrupt the lipid bilayers of the stratum corneum.…”

Optimization of Iontophoretic Parameters for the Transdermal Delivery of Methotrexate

“…Previously various formulation strategies and enhancement techniques have been used to enhance the transdermal delivery of MTX (Vaidyanathan, Chaubal, and Vassarada 1985;Alvarez-Figueroa, Delgado-Charro, and Blanco-Mendez 2001;Sutton et al 2001;Wong et al 2005;Vemulapalli et al 2008). Tiwari et al (2003) studied the clinical efficacy of MTX by means of iontophoresis and suggested that a short application of current is sufficient for the treatment of psoriasis.…”

Transdermal Delivery of Proteins

“…Application of iontophoresis on pretreated skin further pushes the charged molecules down these pathways and into the deeper layers of the skin. This combination approach has been reported to increase drug delivery by several fold (29,(86)(87)(88). For example, Daniplestim, a peptide with a molecular weight of 13 kDa was shown to have higher delivery levels after the combination treatment as compared with iontophoresis alone (87).…”