Huang Shao-Ling, Kee Patrick H, Kim Hyunggun, Moody Melanie R, Chrzanowski Stephen M, Macdonald Robert C, McPherson David D
Division of Cardiology, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
J Am Coll Cardiol. 2009 Aug 11;54(7):652-9. doi: 10.1016/j.jacc.2009.04.039.
We sought to develop a new bioactive gas-delivery method by the use of echogenic liposomes (ELIP) as the gas carrier.
Nitric oxide (NO) is a bioactive gas with potent therapeutic effects. The bioavailability of NO by systemic delivery is low with potential systemic effects.
Liposomes containing phospholipids and cholesterol were prepared by the use of a new method, freezing under pressure. The encapsulation and release profile of NO from NO-containing ELIP (NO-ELIP) or a mixture of NO/argon (NO/Ar-ELIP) was studied. The uptake of NO from NO-ELIP by cultured vascular smooth muscle cells (VSMCs) both in the absence and presence of hemoglobin was determined. The effect of NO-ELIP delivery to attenuate intimal hyperplasia in a balloon-injured artery was determined.
Coencapsulation of NO with Ar enabled us to adjust the amount of encapsulated NO. A total of 10 microl of gas can be encapsulated into 1 mg of liposomes. The release profile of NO from NO-ELIP demonstrated an initial rapid release followed by a slower release during the course of 8 h. Sixty-eight percent of cells remained viable when incubated with 80 microg/ml of NO/Ar-ELIP for 4 h. The delivery agent of NO to VSMCs by the use of NO/Ar-ELIP was 7-fold greater than unencapsulated NO. We discovered that NO/Ar-ELIP remained an effective delivery agent of NO to VSMCs even in the presence of hemoglobin. Local NO-ELIP administration to balloon-injured carotid arteries attenuated the development of intimal hyperplasia and reduced arterial wall thickening by 41 +/- 9%.
Liposomes can protect and deliver a bioactive gas to target tissues with the potential for both visualization of gas delivery and controlled therapeutic gas release.
我们试图通过使用超声造影脂质体（ELIP）作为气体载体来开发一种新的生物活性气体递送方法。
一氧化氮（NO）是一种具有强大治疗作用的生物活性气体。全身递送时，NO的生物利用度较低且存在潜在的全身效应。
采用一种新方法，即压力冷冻法制备含有磷脂和胆固醇的脂质体。研究了含NO的ELIP（NO-ELIP）或NO/氩气混合物（NO/Ar-ELIP）中NO的包封和释放情况。测定了在有无血红蛋白存在的情况下，培养的血管平滑肌细胞（VSMC）对NO-ELIP中NO的摄取。确定了NO-ELIP递送对减轻球囊损伤动脉内膜增生的作用。
将NO与氩气共包封使我们能够调节包封的NO量。总共10微升气体可被包封到1毫克脂质体中。NO-ELIP中NO的释放情况显示，最初快速释放，随后在8小时内缓慢释放。当与80微克/毫升的NO/Ar-ELIP孵育4小时时，68%的细胞仍保持活力。使用NO/Ar-ELIP向VSMC递送NO的效率比未包封的NO高7倍。我们发现，即使在有血红蛋白存在的情况下，NO/Ar-ELIP仍然是向VSMC递送NO的有效载体。对球囊损伤的颈动脉局部给予NO-ELIP可减轻内膜增生的发展，并使动脉壁增厚减少41±9%。
脂质体可以保护生物活性气体并将其递送至靶组织，具有可视化气体递送和可控治疗性气体释放的潜力。
