Department of Biomedical Engineering, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva, 84105, Israel.
Ann Biomed Eng. 2009 Dec;37(12):2640-5. doi: 10.1007/s10439-009-9785-z.
Administration of drugs using small (<100 nm) unilamellar liposomes enables effective targeting of tumors and inflamed tissue. Therapeutic efficacy may be enhanced by triggering liposomal drug release in the desired organ in a controlled manner using a noninvasive external signal. Previous studies have demonstrated that low frequency ultrasound (LFUS) can be used to control the release of drugs from liposomes. LFUS irradiation has a twofold effect: (1) it causes the impermeable liposome membrane to become permeable and (2) it induces liposome disintegration. Immediately upon cessation of LFUS irradiation the membrane resumes its impermeable state and liposome disintegration stops. The mathematical model presented here is aimed at providing a better quantitative and qualitative understanding of LFUS-induced liposomal drug release, which is essential for safe and effective implementation of this technique. The time-dependent release patterns are determined by the liposome disintegration patterns and by two key parameters: (a) the average permeability of the membrane to the drug and (b) the ratio between the volume of the entire dispersion and the initial volume of all the liposomes in the dispersion. The present model implies that LFUS irradiation triggers two liposomal drug-release mechanisms: the predominant one is diffusion through the LFUS-compromised liposome membrane, and the less significant one is liposome disintegration.
使用小于 100nm 的单层小脂质体给药能够有效靶向肿瘤和炎症组织。通过使用非侵入性外部信号以可控的方式在所需器官中触发脂质体药物释放，可以增强治疗效果。先前的研究已经证明，低频超声（LFUS）可用于控制脂质体中药物的释放。LFUS 辐射具有双重作用：（1）使不可渗透的脂质体膜变得可渗透；（2）诱导脂质体崩解。一旦停止 LFUS 辐射，膜就会恢复其不可渗透的状态，并且脂质体崩解停止。本文提出的数学模型旨在提供对 LFUS 诱导的脂质体药物释放的更好的定量和定性理解，这对于安全有效地实施该技术至关重要。时间依赖性释放模式由脂质体崩解模式和两个关键参数决定：（a）药物通过膜的平均渗透率；（b）整个分散体的体积与分散体中所有脂质体的初始体积之比。该模型表明，LFUS 辐射触发了两种脂质体药物释放机制：主要机制是通过 LFUS 损伤的脂质体膜扩散，次要机制是脂质体崩解。
