Thermoresponsive Drug Delivery Using Liquid Crystal-Embedded Cellulose Nitrate Membranes

Abstract

The aim of this study was to investigate the use of thermotropic liquid crystalline (TLC) blends of 4-pentyl-4′-cyanobiphenyl (K15) and 4-heptyl-4′-cyanobiphenyl (K21) with appropriate nematic to isotropic phase temperature (Tn − i) just above body temperature as a temperature-modulated drug permeation system. Using differential scanning calorimetry (DSC) we showed that the phase transition temperature (Tn − i) of K15 and K21 were 34.2°C and 41.5°C respectively. However, the thermogram of K15 and K21 blends with different ratios was shown to be a single endothermic peak similar to that of pure TLCs. K15 and K21 blends did not behave as a physical blend of two thermotropic liquid crystals with different Tn − i. However, they are rather mixed together in such ways that behave like a single unit TLC. The Tn − i of these TLC mixtures was linearly proportionate to the ratio of K15:K21. Using appropriate ratio of K15:K21 TLC, a mixture with desirable phase transition temperature was obtained. A triple layer of cellulose nitrate membranes containing a 50:50 mixture of K15 and K21 was used for drug permeation studies. This composite membrane showed good pulsatile permeation of drug molecules in response to temperature changes below and above the Tn − i of the K15 and K21 blends in a reproducible and reversible manner. Paracetamol and methimazole were chosen as hydrophobic and hydrophilic drug models, respectively. Methimazole permeability through the TLC membrane was much higher (36.0 × 10−5 cm/s) at temperatures above the phase transition temperature of liquid crystal blends than that (7.2 × 10−5 cm/s) at temperatures below the phase transition temperature of liquid crystal blends (38.1°C).