Novel in situ forming hydrogel microneedles for transdermal drug delivery

Abstract

Novel in situ forming hydrogel microneedles were evaluated for transdermal drug delivery using a biocompatible non-ionic triblock amphiphilic thermosensitive copolymer. The transition property of poloxamer from solution at room temperature to gel at skin temperature (32 °C) was utilized in preparation of in situ forming hydrogel microneedles. Methotrexate has been used to treat solid tumors, but because of its narrow safety margin, it requires sustained delivery within the therapeutic window. Formulations with and without poloxamer at different methotrexate concentrations were prepared and evaluated for drug permeation across skin using vertical Franz diffusion cell for 72 h. Sol-gel transition, skin resistance and thickness, microneedles geometry, microchannel depth, shape, formation and uniformity, viscoelasticity of skin, and in vitro drug permeation were characterized and tested. An average cumulative drug amount of 32.2 ± 15.76 and 114.54 ± 40.89 μg/cm² for porcine ear skin and 3.89 ± 0.60 and 10.27 ± 6.98 μg/cm² for dermatomed human skin from 0.2 % w/w and 0.4 % w/w methotrexate formulations was delivered by the in situ forming hydrogel microneedles. These in situ hydrogel microneedles embedded within the porated site of the skin provided a steady and sustained drug delivery.

Keywords: In situ hydrogel; Microneedle; biocompatible; methotrexate; poloxamer; transdermal drug delivery.