I.N.B.B. Consortium, Roma, Italy.
Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy.
J Pharm Pharmacol. 2017 Sep;69(9):1091-1098. doi: 10.1111/jphp.12754. Epub 2017 Jun 16.
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.
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.
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.
Variation of LAA portion can modulate the naproxen prodrugs affinity towards the biological membrane as well as towards the lipophilic carrier.
研究用于治疗阿尔茨海默病的非甾体抗炎药萘普生与脂氨基酸（LAA）直接或通过二乙胺（EDA）间隔物缀合，以提高药物的亲脂性并增强与磷脂双层的相互作用。
通过差示扫描量热法研究了萘普生及其前药与由二肉豆蔻酰磷脂酰胆碱多层囊泡组成的生物膜模型的相互作用。还研究了前药从亲脂载体向生物膜模型的转移。
萘普生与脂氨基酸的缀合可改善其与生物膜模型的相互作用，并影响从亲脂载体向生物膜模型的转移。LAA 部分可能位于磷脂链之间；相互作用的程度不仅取决于间隔物的存在，还取决于 LAA 链长。
LAA 部分的变化可以调节前药对生物膜以及亲脂载体的亲和力。
