Lattin James R, Pitt William G
Chemical Engineering Department, Brigham Young University, Provo, Utah, 84602.
J Pharm Sci. 2015 Apr;104(4):1373-84. doi: 10.1002/jps.24344. Epub 2015 Jan 11.
Liposomes containing emulsion droplets (eLiposomes) were studied as ultrasound-responsive liposomal drug carriers. This paper presents the effects of temperature, eLiposome size, and ultrasound parameters on the ultrasonically actuated release of calcein, to test hypotheses concerning the physics of acoustic droplet vaporization with regard to vapor pressure and Laplace pressure. Small (200 nm) eLiposomes containing 100-nm emulsion droplets were formed and compared with large (800 nm) eLiposomes containing 100- or 450-nm droplets. Calcein release was quantified by spectroscopic methods. Various experiments examined the influence of perfluorocarbon (PFC) droplet size, vesicle size, temperature, PFC composition and vapor pressure, insonation time, and insonation frequency. Results showed that eLiposome samples released significantly more calcein than their conventional liposome counterparts. Surprisingly, temperature (which directly controls vapor pressure) did not have a strong effect on ultrasound-induced calcein release. In general, calcein release decreased with decreasing droplet size, as hypothesized based on Laplace pressure. Release decreased with increased ultrasound frequency if the pressure amplitude and exposure time were maintained constant, indicating that the gas-phase nucleation rate may have an important role in rupture of eLiposomes. Interestingly, when ultrasound of the same mechanical index was applied at two frequencies, the amount of release correlated strongly with the mechanical index.
含有乳液滴的脂质体（e脂质体）作为超声响应性脂质体药物载体进行了研究。本文介绍了温度、e脂质体大小和超声参数对钙黄绿素超声驱动释放的影响，以检验关于声滴蒸发物理过程中蒸气压和拉普拉斯压力的假设。制备了含有100nm乳液滴的小（200nm）e脂质体，并与含有100nm或450nm液滴的大（800nm）e脂质体进行比较。通过光谱方法对钙黄绿素的释放进行定量。各种实验研究了全氟化碳（PFC）液滴大小、囊泡大小、温度、PFC组成和蒸气压、超声照射时间和超声照射频率的影响。结果表明，e脂质体样品比传统脂质体释放出显著更多的钙黄绿素。令人惊讶的是，直接控制蒸气压的温度对超声诱导的钙黄绿素释放没有强烈影响。一般来说，如基于拉普拉斯压力所假设的那样，钙黄绿素释放随着液滴大小的减小而降低。如果压力幅度和暴露时间保持恒定，释放量会随着超声频率的增加而降低，这表明气相成核速率可能在e脂质体破裂中起重要作用。有趣的是，当在两个频率下施加相同机械指数的超声时，释放量与机械指数密切相关。
