Devaraj Gopi N, Parakh S R, Devraj Ravi, Apte S S, Rao B Ramesh, Rambhau D
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506 009, India.
J Colloid Interface Sci. 2002 Jul 15;251(2):360-5. doi: 10.1006/jcis.2002.8399.
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 C(16+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.
一些两亲分子的单体组装成双层结构以形成脂质体和非离子表面活性剂泡囊。这种双层结构不稳定或有渗漏，因此胆固醇是一种常用的添加成分来使其稳定。胆固醇可稳定双层结构，防止渗漏，并延缓包裹在这些囊泡水相核心中的溶质渗透。除胆固醇外，尚未发现具有良好双层稳定性能的材料。我们在含有聚甘油-3-二异硬脂酸酯（PGDS）和聚山梨酯-80（PS-80）的非离子表面活性剂泡囊中用脂肪醇替代胆固醇，通过渗透研究来探索它们的膜稳定性能。采用乙醚注入法制备了聚甘油-3-二异硬脂酸酯、脂肪醇/胆固醇和聚山梨酯的非离子表面活性剂泡囊。将酮咯酸氨丁三醇（KT）的水溶液包封在其中。通过改进的溶出-透析法评估了脂肪醇（C(12)、C(14)、C(16)、C(18)和C(16 + 18)）的烷基链长度、聚氧乙烯山梨醇单酯表面活性剂的酰基链长度以及脂质混合物的摩尔比对非离子表面活性剂泡囊中酮咯酸释放速率的影响。含有胆固醇或脂肪醇的非离子表面活性剂泡囊呈现出共同的释放模式。含有脂肪醇的非离子表面活性剂泡囊显示出的KT释放速率比含有胆固醇的泡囊慢得多。基于释放速率，脂肪醇的排序为：硬脂醇＜肉豆蔻醇＜十六醇＜月桂醇＜鲸蜡硬脂醇。在含有PGDS、肉豆蔻醇（MA）和聚山梨酯的非离子表面活性剂泡囊中，聚氧乙烯山梨醇酯型表面活性剂的脂肪酸链长度影响了释放速率和包封率。基于释放速率，聚山梨酯的排序为：聚山梨酯-20（C(12)）＜聚山梨酯-60（C(18)）＜聚山梨酯-80（C(9 = 9)）＜聚山梨酯-40（C(16)）。在含有聚山梨酯-20和磺基琥珀酸二辛酯钠（一种阴离子表面活性剂）的非离子表面活性剂泡囊制备中，释放速率比含有聚山梨酯-20的泡囊慢。当MA浓度保持在50摩尔%不变且改变PGDS与PS-80的比例时，观察到包封率和释放速率有显著变化。然而，该比例与包封率或释放速率没有任何关系。释放速率和包封率呈负相关（对于PGDS:MA:PS80摩尔比的数据，r(2)=0.8774，p＜0.02；对于聚山梨酯酰基链长度变化的数据，r(2)=0.975，p＜0.001）。可以得出结论，可用脂肪醇和聚山梨酯替代胆固醇制备稳定的聚甘油-3-二异硬脂酸酯非离子表面活性剂泡囊，并且通过改变膜成分及其浓度可以优化这些非离子表面活性剂泡囊中溶质的释放。
