A class of intelligent thermo-sensitive membranes was synthesized by immobilizing the thermo-sensitive polymeric gel, poly(N-isopropylacrylamide) (PNIPAAM) or PNIPAAM-co-2 mol% acrylic acid (AA) on the surface and inside the pores of a hydrophilized polyvinylidene fluoride (PVDF) membrane, hereafter referred to as PNIPAAM-PVDF membrane or 2%AA-PVDF membrane, respectively. Such gel-modified membranes have drastically different permeation properties upon the volume-phase transition of the immobilized gel at its lower critical solution temperature (LCST). The permeability and flux of 2%AAPVDF membrane at its LCST (33 degrees C) almost doubled compared to those at 32 degrees C for the agent doxycycline HCl partitioning from its solution/dispersion in light mineral oil in the donor reservoir bounded by the membrane. Further in vitro studies with a mouse skin mounted beneath the 2%AA-PVDF membrane demonstrated that its release can be switched on and off at the LCST of the gel. At 32 degrees C, there was no doxycycline HCl release through skin for 24 h, while at 33 degrees C, the ailing condition, 30 mu g/cm(2) of doxycycline HCl was accumulated in the receptor through the skin after 24 h with the permeability and flux being very close to those from a regular PVDF/mouse skin composite. Since human skin temperature changes from 32 degrees C to 33 degrees C under certain feverish conditions, the gel-modified membranes can be exploited as a transdermal control led-re lease system for treating fever symptoms. However, for smaller molecules such as caffeine, different configurations yielded almost the same permeation profiles. (C) 2009 Elsevier B.V. All rights reserved.