Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone
Physicochemical properties of extruded and non-extruded liposomes containing the hydrophobic drug dexamethasone
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DOI：
10.1016/j.ijpharm.2010.01.003
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发表时间：
2010-03-30
影响因子：
5.8
通讯作者：
Burgess, Diane J.
中科院分区：
文献类型：
--
作者：
Bhardwaj, Upkar;Burgess, Diane J.
研究了非挤出型“多层”和超声-挤出型1，2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）、1，2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）和1，2-二硬脂酰-sn-甘油-3-磷酸胆碱（DSPC）疏水药物地塞米松脂质体的理化性质和释放特性。非挤出脂质体具有相似的直径，但是地塞米松包封随着脂质链长度的增加而减少。地塞米松使脂质体膜不稳定，如焓降低和主跃迁峰宽增加所示。基于量热分析，地塞米松和胆固醇似乎不均匀地分布在非挤出脂质体中。超声处理和挤出减小了直径（DSPC > DPPC > DMPC）并减少了药物包封（约50%）。胆固醇掺入减少药物包封在挤出和非挤出DMPC脂质体，这似乎是由于胆固醇和地塞米松之间的结构相似性。地塞米松和胆固醇在同一DMPC脂质体中的掺入引起相变的显著扰动。地塞米松从挤出脂质体释放快，而非挤出脂质体显示较慢的释放。DMPC脂质体释放最快，高相变脂质DSPC脂质体释放最慢。胆固醇的掺入并不降低DMPC脂质体的释放。这些结果表明，由于加工以及疏水药物地塞米松的掺入，脂质体的理化性质和相变行为的变化，改变了它们的释放特性。(C)2010爱思唯尔有限公司版权所有。
The physicochemical and release properties of non-extruded 'multilamellar' and small sonicated and extruded 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposomes containing hydrophobic drug dexamethasone were investigated. Non-extruded liposomes had similar diameter, however dexamethasone encapsulation decreased with increase in lipid chain length. Dexamethasone destabilized the liposome membranes as indicated by decrease in enthalpy and increase in the peak width of the main transition. Based on calorimetric analysis, it appeared that dexamethasone and cholesterol were heterogeneously distributed in the non-extruded liposomes. Sonication and extrusion reduced the diameter (DSPC > DPPC > DMPC) and decreased drug encapsulation (approximately 50%). Cholesterol incorporation decreased drug encapsulation in both extruded and non-extruded DMPC liposomes which appeared to be due to structural similarities between cholesterol and dexamethasone. Incorporation of dexamethasone and cholesterol in the same DMPC liposomes caused a marked perturbation in the phase transition. Dexamethasone release from extruded liposomes was fast, while non-extruded liposomes showed slower release. Release was fastest from DMPC liposomes and slowest from liposomes of high phase transition lipid DSPC. Incorporation of cholesterol did not decrease release from DMPC liposomes. These results indicated that change in the physicochemical properties and the phase transition behavior of liposomes, due to processing as well as incorporation of hydrophobic drug dexamethasone, changed their release properties. (C) 2010 Elsevier B.V. All rights reserved.