功能性磷脂的合成及剪切力敏感型脂质体的制备

Synthesis of functional phospholipids and preparation of shear-stress sensitive liposomes

本研究拟合成新型磷脂材料1,3-二棕榈酰胺磷脂酰胆碱(1,3-dipalmaminophospholipid,Pad-PC-Pad),并制备剪切力敏感型脂质体(shear-stress sensitive liposomes,SSSL)。首先,化学合成了新型磷脂材料Pad-PC-Pad,核磁和质谱的表征结果表明合成成功;其次,以Pad-PC-Pad为膜材,采用薄膜水化分散法制备了剪切力敏感型脂质体,并包载具有聚集淬灭(aggregation-caused quenching,ACQ)特性的荧光染料钙黄绿素对制剂在狭窄部位的剪切力敏感性和释放特性进行了考察。结果表明:脂质体粒径为106.91±1.24 nm,在透射电镜下呈椭球形。脂质体随超声功率增加内含物释放增加,表明该载体具备剪切力敏感性。另外,脂质体在狭窄部位受高剪切力作用,具有快速释放特性。本研究合成了一种功能性磷脂Pad-PC-Pad,该磷脂制备的脂质体具备剪切力敏感性,有望用于血栓部位的特异性治疗。

This study aims to synthesize new phospholipids, 1,3-dipalmaminophospholipid（Pad-PC-Pad）, and prepare shear-stress sensitive liposomes（SSSL）. 1H NMR and MS indicated that Pad-PC-Pad were fully synthesized successfully. SSSL were prepared by filming-rehydration method with Pad-PC-Pad, which loaded calcein with aggregation-caused quenching（ACQ） characteristics to evaluate shear-stress sensitivity of liposomes and release behavior of liposomes in vitro. The results showed that the particle size of liposomes was 106.91 ± 1.24 nm and liposomes had lenticular morphology under transmission electron microscope. The release of calcein was increased with ultrasonic power, which suggests that the liposomes is shear-stress sensitive. Moreover, the liposomes exhibited a releasing effect for obstructed region under high shear-stress in a model system. Therefore, we synthesized quick functional phospholipid Pad-PC-Pad and the liposomes made from Pad-PC-Pad was shear-stress sensitive, which may be used for treatment of thrombosis.