Interaction of naproxen amphiphilic derivatives with biomembrane models evaluated by differential scanning calorimetry and Langmuir–Blodgett studies

Anti-inflammatory drugs represent a potential new strategy for the treatment of Alzheimer’s disease (AD). The ability to cross the blood–brain barrier and to reach brain tissues is a critical point for these drugs and is strictly related to their lipophilicity. Naproxen (NAP) is a non-steroidal anti-inflammatory drug (NSAIDs) under active investigation for AD. To improve its lipophilic character, NAP was conjugated through a diethylamine spacer (EDA) to lipoamino acids (LAA), α-amino acids containing a long alkyl side chain, to obtain the NAP–EDA–LAA10 and NAP–EDA–LAA14 prodrugs. The interaction of NAP and prodrugs with dimyristoylphosphatidylcholine phospholipids, forming either multilamellar vesicles or monolayers (at the air/water interface) and used as biomembrane models, was studied by differential scanning calorimetry and Langmuir–Blodgett techniques. Experimental data showed that NAP conjugation with LAA residues was able to enhance the drug interaction with such biomembrane models.