Acoustically active liposomes for drug encapsulation and ultrasound-triggered release
Acoustically active liposomes for drug encapsulation and ultrasound-triggered release
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DOI：
10.1016/j.bbamem.2004.07.003
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发表时间：
2004-10-11
影响因子：
3.4
通讯作者：
MacDonald, RC
中科院分区：
文献类型：
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作者：
Huang, SL;MacDonald, RC
以前作为超声造影剂开发的声学活性脂质体(AAL)含有少量空气。这些AAL具有携带药物的潜力，它们的声学活性可以使它们通过释放其内容物来对超声波刺激做出反应。由于脂质体可以包裹许多种药物，如果这种包裹不影响它们的回声，那么内容物的释放可能可以通过超声波刺激来控制。本研究的目的是考察具有声学活性的脂质体对亲水性分子的包封性，并测定其对超声触发释放的敏感性。由磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰甘油和胆固醇组成的脂质体通过使脂膜水化、超声、在甘露醇存在下冷冻、冷冻干燥和再水化来获得声学活性。作为测试分子，钙黄绿素被加入到水合步骤中。制备声学活性脂质体的过程与15%或更高的包封率是兼容的。在冷冻干燥过程中，甘露醇的存在不仅对声学活性的产生至关重要，而且对有效的包埋也是必不可少的。采用频率为1 MHz、功率为2 W/cm(2)的超声波作用10 S，加入4%二庚烷磷脂酰胆碱(DHPC)可提高脂质体对超声刺激的敏感性，并产生非常有效的内容物刺激释放(10 S释放1/3，6次释放2/3)。内容物的释放与超声波或快速降压引起的空气损失高度相关。这些包埋和触发释放技术是高效的，因此可能适用于药物输送。(C)2004爱思唯尔B.V.保留所有权利。
Acoustically active liposomes (AAL), previously developed as ultrasound contrast agents, contain small amounts of air. These AAL have potential to carry pharmaceutics and their acoustic activity could enable them to respond to ultrasound stimulation by releasing their contents. Since liposomes can entrap many kinds of drugs, if such entrapment did not affect their echogenicity, then the release of contents could potentially be controlled by ultrasound stimulation. The aim of this research was to investigate the capacity of acoustically active liposomes for hydrophilic molecule encapsulation and to determine their sensitivity to ultrasound-triggered release. Liposomes, composed of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, and cholesterol, were made acoustically active by hydrating a lipid film, sonication, freezing in the presence of mannitol, lyophilization, and rehydration. As a test molecule, calcein was added in the hydration step. The procedure for generating acoustically active liposomes was compatible with an encapsulation efficiency of 15% or more. The presence of mannitol during freeze-drying was essential not only for generation of acoustic activity but also for efficient encapsulation. Ultrasound-triggered release was achieved by applying 1 MHz ultrasound at 2 W/cm(2) for 10 s. The inclusion of 4% diheptanolyphosphatidylcholine (DHPC) increased the sensitivity of liposomes to ultrasound stimulation and resulted in very efficient stimulated release of contents (1/3 released in 10 s, 2/3 released in six such applications). Release of contents was highly correlated with the loss of air induced either by ultrasound or rapid pressure reduction. These encapsulation and triggered release techniques are highly efficient, and hence may be applicable to drug delivery. (C) 2004 Elsevier B.V. All rights reserved.