Factors affecting acoustically triggered release of drugs from polymeric micelles
Factors affecting acoustically triggered release of drugs from polymeric micelles
复制标题
DOI：
10.1016/s0168-3659(00)00278-9
复制
发表时间：
2000-10-03
影响因子：
10.8
通讯作者：
Rapoport, NAY
中科院分区：
文献类型：
--
作者：
Husseini, GA;Myrup, GD;Rapoport, NAY
使用具有实时荧光检测的定制超声暴露室来测量在20至90 kHz的频率范围内的连续波（CW）或脉冲超声下从Pluronic P-105胶束的声学触发的药物释放。测量是基于当药物从胶束核心转移到水性环境时荧光强度的降低。使用两种荧光药物：阿霉素（DOX）及其顺磁性类似物，ruboxyl（Rb）。使用在水溶液中的各种浓度的Pluronic P-105作为胶束形成聚合物。药物释放是最有效的，在20 kHz的超声和下降，尽管更高的功率密度与超声频率的增加。这些数据表明，在药物释放的瞬态空化的重要作用。DOX的释放高于Rb的释放，这是由于更强的相互作用和Rb更深地插入胶束的核心。药物释放较高，在较低的普朗尼克浓度，这可能是由于较高的局部药物浓度的核心普朗尼克胶束时，胶束的数量是低的。在恒定频率下，药物释放随着功率密度的增加而增加。在恒定的功率密度和脉冲持续时间大于0.1秒，峰值释放下脉冲超声是相同的平稳释放下CW超声。释放的药物在超声脉冲之间迅速重新包封，这表明在离开超声处理体积时，未外渗和未内化的药物将以包封形式循环，从而防止不需要的药物与正常组织的相互作用。(C)2000 Elsevier Science B. V.保留所有权利。
A custom ultrasonic exposure chamber with real-time fluorescence detection was used to measure acoustically-triggered drug release from Pluronic P-105 micelles under continuous wave (CW) or pulsed ultrasound in the frequency range of 20 to 90 kHz. The measurements were based on the decrease in fluorescence intensity when drug was transferred from the micelle core to the aqueous environment. Two fluorescent drugs were used: doxorubicin (DOX) and its paramagnetic analogue, ruboxyl (Rb). Pluronic P-105 at various concentrations in aqueous solutions was used as a micelle-forming polymer. Drug release was most efficient at 20-kHz ultrasound and dropped with increasing ultrasonic frequency despite much higher power densities. These data suggest an important role of transient cavitation in drug release. The release of DOX was higher than that of Rb due to stronger interaction and deeper insertion of Rb into the core of the micelles. Drug release was higher at lower Pluronic concentrations, which presumably resulted from higher local drug concentrations in the core of Pluronic micelles when the number of micelles was low. At constant frequency, drug release increased with increasing power density. At constant power density and for pulse duration longer than 0.1 s, peak release under pulsed ultrasound was the same as stationary release under CW ultrasound. Released drug was quickly re-encapsulated between the pulses of ultrasound, which suggests that upon leavings the sonicated volume, the non-extravasated and non-internalized drug would circulate in the encapsulated form, thus preventing unwanted drug interactions with normal tissues. (C) 2000 Elsevier Science B.V. All rights reserved.