Nanogel particulates located within diffusion cell receptor phases following topical application demonstrates uptake into and migration across skin

Despite growing evidence in support of nanogels as carriers in topical drug delivery, no empirical evidence has been forthcoming regarding a mechanism. Poly(N-isopropylacrylamide-copolymerized-acrylic acid) referred to as poly(NIPAM-co-AAc) and poly(N-isopropylacrylamide) known as (polyNIPAM) nanogels were synthesized by a surfactant-free emulsion polymerisation method and applied to porcine ear skin mounted in Franz diffusion cells. After 24 h the receptor phases were retrieved and scrutinized by transmission electron microscopy (TEM). The skin membranes were also recovered and re-used to determine the permeation of a model permeant, methotrexate (MTX). TEM images confirmed the presence of nanoparticulates in the receptor phases, and the relative quantities varied on the nature of the nanogel. Comparative MTX skin permeation data demonstrated the integrity of the membranes, and that delivery of nanogel or MTX was not due to defects in the membranes. In summary, the first direct evidence is presented demonstrating that nanogels are taken up by and migrate across the skin.