Amphiphilic naproxen prodrugs: differential scanning calorimetry study on their interaction with phospholipid bilayers

This is the authors' abstract. We don't add key points for this paper.

OBJECTIVES: Naproxen, a nonsteroid anti-inflammatory drug studied for Alzheimer's disease, was conjugated with lipoamino acids (LAA) directly or through a diethylamine (EDA) spacer to improve the drug lipophilicity and the interaction with phospholipid bilayers. METHODS: The interaction of naproxen and its prodrugs with biomembrane models consisting of dimyristoylphosphatidylcholine multilamellar vesicles was studied by differential scanning calorimetry. The transfer of prodrugs from a lipophilic carrier to a biomembrane model was also studied. KEY FINDINGS: Naproxen conjugation to lipoamino acids improves its interaction with biomembrane models and affects the transfer from a lipophilic carrier to biomembrane model. LAA portion may localize between the phospholipid chains; the entity of the interaction depends not only on the presence of the spacer but also on the LAA chain length. CONCLUSIONS: Variation of LAA portion can modulate the naproxen prodrugs affinity towards the biological membrane as well as towards the lipophilic carrier.