Temperature modulated drug permeation through liquid crystal embedded cellulose membranes

Stimuli-sensitive membranes may act as "on-off switches" or "permeability valves", producing patterns of pulsatile release, where the period and rate of mass transfer can be controlled by external or environmental triggers. In this study, cellulose nitrate (CN) and cellulose acetate (CA) monolayer membranes containing thermotropic liquid crystals (LC) were developed as thermoresponsive barriers for drug permeation. A low molecular thermotropic LC, n-heptyl-cyanobiphenyl (K21), with nematic to isotropic phase transition temperature (Tn-i) of 41.5 degrees C was chosen to modulate drug permeation. Methimazole and paracetamol as hydrophilic and hydrophobic drug models were used, respectively. It was found that upon changing the temperature of the system around the Tn-i, both cellulose membranes without LC showed no temperature sensitivity to drug permeation, whereas the results for LC entrapped membranes exhibited a distinct jump in permeability when temperature was raised to above the Tn-i of the liquid crystal for both drug models. On the other hand, drug permeation through these LC embedded membranes can be thermally modulated. Thermoresponsive drug permeation through the membranes was reversible, reproducible and followed zero order kinetics. Liquid crystal embedded cellulose acetate membranes showed more temperature sensitivity than liquid crystal embedded cellulose nitrate membranes, apparently due to higher LC loading in their porous matrix compared to CN membranes. The pattern of on-off permeation through LC embedded membranes was more distinguished for methimazole compared to that of paracetamol, seemingly due to its lower molecular weight. (C) 2007 Elsevier B.V. All rights reserved.