Interaction of meloxicam derivatives with phosphatidylcholine bilayers: A calorimetric study

The drug interactions with the lipid membranes are crucial in many biochemical processes. Phospholipid model membranes are often used to assess such interactions. Our team has been researching new compounds with anti-inflammatory and analgesic effects for many years. Such compounds are derivatives of the well-known non-steroidal anti-inflammatory drug (NSAID) - meloxicam (MLX). Their biological target is cyclooxygenase (COX) - a membrane protein. The NSAIDs are mainly taken orally; therefore, drug-membrane interaction is a preliminary stage in the body.

The purpose of the present work was to investigate the ability of 2 new MLX derivatives (compound PR51 and PR52) to interact with model membranes, in comparison to known NSAIDs medicine - MLX. The differential scanning calorimetry (DSC) method was used to study those interactions. As a model membrane, bilayers obtained from a phospholipid (1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC)) were used.

Calorimetric measurements were performed using a differential scanning calorimeter DSC 214 Polyma equipped with an intracooler IC70.

All examined compounds decreased the main transition temperature of DPPC in a concentration-dependent manner. The addition of studied compounds to DPPC also resulted in broadening of the transition peaks. Moreover, all examined compounds decreased the enthalpy of the DPPC main phase transition. For all DPPC gel-liquid crystalline phase transition parameters, the most pronounced effects were found for PR51 compound.

We have shown that the above interactions depend on the chemical structure of individual compound. All studied compounds alter biophysical properties of phospholipid bilayer.