Enhancement of the phase transition permeability of DPPC liposomes by incorporation of MPPC: A new temperature-sensitive liposome for use with mild hyperthermia
Enhancement of the phase transition permeability of DPPC liposomes by incorporation of MPPC: A new temperature-sensitive liposome for use with mild hyperthermia
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DOI：
10.3109/08982109909035549
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发表时间：
1999-01-01
影响因子：
4.4
通讯作者：
Needham, D
中科院分区：
文献类型：
--
作者：
Anyarambhatla, GR;Needham, D
本研究提出了一种新的制备温敏性脂质体的方法，即在1，2-双丙氨酰基-3-甘油-3-磷胆碱(1-Palmitoyl-2-Hydroxy-sn-Glycero-3-Phosphocholine)凝胶相脂质体中掺入一种具有高度双层相容性的伊索磷脂(DPPC)。与在40-45摄氏度范围内仅释放20%内容物的纯DPPC以及在43-45摄氏度范围内释放较慢的更传统的(基于DPPC/DSPC的)温度敏感型脂质体相比，脂质体的这种成分修饰在39-40摄氏度的温和高温下显著提高了包埋的脂质体内容物的释放。此外，DPPC：MPPC系统发生最大释放的温度范围仍然非常窄，仅在数十秒的加热后就达到了最大释放。通过研究不同温度和时间间隔下脂质体中羧基荧光素的释放情况，对脂质体制剂进行了表征。用相同成分的差示扫描量热法对制剂的累积释放曲线进行关联，以了解与包埋标志物释放相关的分子机制。考察了磷酸盐缓冲盐水和人血清白蛋白对脂质体的稳定性和热敏感性。这里提出的触发释放的新概念是，当凝胶相脂质体的温度上升到39℃-40℃时，随着第一脂类开始融化，MPPC从液相区解吸，产生增强的缺陷形成，从而显著增加膜脂对被包裹的CF的渗透性。
The present study describes a novel method of preparing thermosensitive liposomes by compositional modification, incorporating a highly bilayer compatible Iysolipid, 1-Palmitoyl-2-Hydroxy-sn-Glycero-3-Phosphocholine (DPPC) into the gel phase liposomes composed of 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC). This compositional modification of the liposomes achieved a significantly enhanced release of entrapped liposome contents at mild hyperthermic temperatures between 39 degrees C-40 degrees C as compared to pure DPPC which released only 20% of contents over a broader range of 40 degrees C-45 degrees C, and the more conventional (DPPC/DSPC-based) temperature-sensitive liposomes that released more slowly in the 43 degrees C-45 degrees C range. Also, the temperature range over which the maximum; release occurred for the DPPC:MPPC system remained very narrow and maximum release is achieved after only a tens of seconds of heating. Characterization of the liposome formulation was carried out by studying the release profiles of entrapped carboxyfluorescein from the liposomes at various temperatures and time intervals. The cumulative release profiles of the formulation were correlated with differential scanning calorimetric scans of the same compositions in order to understand the molecular mechanisms associated with the release of entrapped marker. The stability and thermal sensitivity of the liposomes in the presence of phosphate buffered saline and human serum albumin were evaluated. The new concept for triggered release presented here is that upon raising the temperature of the gel phase liposome to 39 degrees C-40 degrees C, the desorption of MPPC from liquid phase regions as the first lipid begins to melt creates enhanced defect formation which dramaticaly increases the permeability of the memrbane to the entrapped CF.