Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol
Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol
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DOI：
10.1006/jcis.2002.8399
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发表时间：
2002-07-15
影响因子：
9.9
通讯作者：
Rambhau, D
中科院分区：
文献类型：
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作者：
Devaraj, GN;Parakh, SR;Rambhau, D
一些两亲体的单体组成双分子层，形成脂质体和乳质体。这种双分子层是不稳定的或有渗漏的，因此胆固醇是一种常用的成分来稳定它们。胆固醇稳定双分子层，防止渗漏，并延缓溶质的渗透被包裹在这些囊泡的水核。除了胆固醇，还有一种具有良好双层稳定性能的材料尚未被发现。我们在含有聚甘油-3-二异硬脂酸酯（PGDS）和聚山梨酸酯-80 （PS-80）的膜小体中用脂肪醇取代胆固醇，通过渗透研究探索它们的膜稳定特性。采用醚注射法制备了聚甘油三酯-3-二异硬脂酸酯、脂肪醇/胆固醇和聚山梨酸酯三种脂质体。其中包埋了酮咯酸三聚氰胺（KT）水溶液。采用改进的溶出-透析法，考察了脂肪醇（C-12、C-14、C-16、C-18和C16+18）的烷基链长、聚氧乙烯山梨糖单酯表面活性剂的酰基链长以及脂质混合物的摩尔比对酮酸释放率的影响。含有胆固醇或脂肪醇的溶酶体表现出共同的释放模式。含有脂肪醇的乳质体比含有胆固醇的乳质体释放KT的速度要慢得多。根据脂肪醇的释放速率，可将其排序为：硬脂酰<肉豆蔻酰<十六烷基<十二烷基<十六烷基硬脂酰。聚氧乙烯山梨醇酯型表面活性剂的脂肪酸链长影响其释放速度和包封效率。根据释放速率，聚山梨酸酯可以排列为：聚山梨酸酯-20 (C-12) <聚山梨酸酯-60 (C-18) <聚山梨酸酯-80 (C-9=9) <聚山梨酸酯-40 （C-16）。在含有聚山梨酸酯-20和二辛基琥珀磺酸钠（阴离子表面活性剂）的纳米体制剂中，释放速度比含有聚山梨酸酯-20的纳米体慢。当MA浓度为50摩尔%时，改变PGDS与PS-80的比例，捕集效率和释放率发生显著变化。然而，该比例与包封效率和释放率没有任何关系。PGDS: MA: PS80的摩尔比数据显示，释放率与包封呈负相关（r(2) = 0.8774, p < 0.02）；聚山梨酯酰基链长变化数据R (2) = 0.975 （p < 0.001）。综上所述，可以用脂肪醇和聚山梨酸酯代替胆固醇制备稳定的聚甘油-3-二异硬脂酸脂质体，并且可以通过改变膜成分及其浓度来优化这些脂质体中溶质的释放。(C) 2002 Elsevier Science （USA）。
Monomers of some amphiphiles organize into bilayers to form liposomes and niosomes. Such bilayers are unstable or leaky and hence cholesterol is a common ingredient included to stabilize them. Cholesterol stabilizes bilayers, prevents leakiness, and retards permeation of solutes enclosed in the aqueous core of these vesicles. Other than cholesterol a material with good bilayer-stabilizing properties is yet to be identified. We have substituted cholesterol with fatty alcohols in niosomes containing polyglyceryl-3-di-isostearate (PGDS) and polysorbate-80 (PS-80) to explore their membrane-stabilizing property via permeation studies. Niosomes of polyglyceryl-3-di-isostearate, fatty alcohol/cholesterol, and polysorbate were prepared by ether injection method. Aqueous solution of ketorolac tromethamine (KT) was entrapped in them. The effects of alkyl chain length of fatty alcohols (C-12, C-14, C-16, C-18, and C16+18), of acyl chain length of polyoxyethylene sorbitan monoester surfactants, and of the molar ratio of lipid mixture on the release rate of ketorolac from niosomes were assessed by employing modified dissolution-dialysis method. Niosomes with cholesterol or fatty alcohols have exhibited a common release pattern. Niosomes containing fatty alcohol showed a considerably slower release rate of KT than those containing cholesterol. Based on the release rate, fatty alcohols can be ranked as stearyl < myristyl < cetyl < lauryl < cetostearyl. In niosomes containing PGDS, myristyl alcohol (MA), and polysorbate, the fatty acid chain length of polyoxyethylene sorbitan ester-type surfactants has influenced the release rate and encapsulation efficiency. Based on the release rate, polysorbates can be ranked as polysorbate-20 (C-12) < polysorbate-60 (C-18) < polysorbate-80 (C-9=9) < polysorbate-40 (C-16). In niosome preparation containing polysorbate-20 and dioctyl sodium sulfosuccinate (anionic surfactant), the release rate was slower than niosomes containing polysorbate-20. When MA concentration is kept constant at 50 mole% and the ratio of PGDS and PS-80 was altered, significant changes in entrapment efficiency and the release rate were observed. However, this ratio did not exhibit any relation with encapsulation efficiency or release rate. The release rate and entrapment exhibited an inverse correlation (r(2) = 0.8774 at p < 0.02 for the data of molar ratios of PGDS: MA: PS80; r(2) = 0.975 at p < 0.001 for the data of acyl chain length variation of polysorbates). It can be concluded that stable niosomes of polyglyceryl-3-di-isostearate could be prepared with fatty alcohols and polysorbates instead of cholesterol and that the release of solutes from these niosomes can be optimized by altering membrane constituents and their concentrations. (C) 2002 Elsevier Science (USA).