A thermo-sensitive release system based on polymeric membrane for transdermal delivery of doxycycline HCl

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%AA-PVDF membrane at its LCST (33 °C) almost doubled compared to those at 32 °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 °C, there was no doxycycline HCl release through skin for 24 h, while at 33 °C, the ailing condition, 30 μg/cm² 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 °C to 33 °C under certain feverish conditions, the gel-modified membranes can be exploited as a transdermal controlled-release system for treating fever symptoms. However, for smaller molecules such as caffeine, different configurations yielded almost the same permeation profiles.