Natural Products Research and Development Center (NPRDC), Science and Technology Research Institute (STRI), Chiang Mai University, Chiang Mai 50200, Thailand.
J Microencapsul. 2010 May;27(3):272-80. doi: 10.3109/02652040903131293.
The objective of this study was to enhance the entrapment of various charged peptide drugs [(bacitracin (BCT), insulin and bovine serum albumin (BSA)] in niosomes by modifying the vesicular charge compositions. Cationic, anionic and neutral niosomes were prepared from sorbitan monostearate (Span 60) or polyoxyethylene sorbitan monostearate (Tween 61), cholesterol (CHL), dimethyldioctadecylammonium bromide (DDAB) and/or dicetyl phosphate (DP) in distilled water, by freeze dried empty liposome (FDEL) method. Morphology and vesicular sizes of the vesicles were investigated by optical microscope, TEM, X-ray diffractometry and dynamic light scattering. The entrapment efficiency of the peptides in niosomes was determined by gel electrophoresis and gel documentation. After reconstitution of the empty niosomal powder in phosphate buffer pH 7.0 containing the peptide drugs, they were oligolamellar membrane structure, with the sizes of 40-60 nm, except the neutral niosomes entrapped with insulin and cationic niosomes entrapped with BSA which showed the sizes of 0.1-1.3 microm and 100-150 nm, respectively. The zeta potential values of neutral, cationic and anionic niosomes entrapped with BSA, insulin and BCT were -22.3 +/- 1.52, -30.7 +/- 2.92 and +22.68+/- 1.31 mV, respectively. The entrapment efficiency of BSA, BCT and insulin in neutral niosomes (Tween 61/CHL at 1 : 1 molar ratio) was 72.94, 69.89 and 10.26%, in cationic niosomes (Tween 61/CHL/DDAB at 1 : 1 : 0.05 molar ratio) was 84.54, 32.85 and 87.15% and in anionic niosomes (Tween 61/CHL/DP at 1 : 1 : 0.05 molar ratio) was 50.13, 90.88 and 44.31%, respectively. The highest entrapment efficiency of BSA, BCT and insulin at 72.94, 90.88 and 87.15 was observed in neutral, anionic and cationic niosomes, respectively. The results from this study has suggested the appropriate niosomal formulation to entrap the peptides with different charges and polarity for pharmaceutical application.
本研究的目的是通过改变囊泡的电荷组成来提高各种带电荷的肽类药物（杆菌肽（BCT）、胰岛素和牛血清白蛋白（BSA））在类脂体中的包封率。阳离子、阴离子和中性类脂体分别由山梨醇单硬脂酸酯（Span 60）或聚氧乙烯山梨醇单硬脂酸酯（Tween 61）、胆固醇（CHL）、二甲基十八烷基溴化铵（DDAB）和/或双十六烷基磷酸酯（DP）在蒸馏水中制备，采用冻干空脂质体（FDEL）法。通过光学显微镜、TEM、X 射线衍射和动态光散射研究了囊泡的形态和囊泡大小。通过凝胶电泳和凝胶文档确定了肽类在类脂体中的包封效率。在磷酸盐缓冲液 pH 7.0 中再构成载有肽类药物的空类脂体粉末后，除了载有胰岛素的中性类脂体和载有 BSA 的阳离子类脂体分别显示出 0.1-1.3 微米和 100-150 纳米的大小外，它们均为寡层膜结构，大小为 40-60nm。载有 BSA、胰岛素和 BCT 的中性、阳离子和阴离子类脂体的 Zeta 电位值分别为-22.3+/-1.52、-30.7+/-2.92 和+22.68+/-1.31 mV。在中性类脂体（Tween 61/CHL 摩尔比为 1:1）中，BSA、BCT 和胰岛素的包封效率分别为 72.94%、69.89%和 10.26%，在阳离子类脂体（Tween 61/CHL/DDAB 摩尔比为 1:1:0.05）中分别为 84.54%、32.85%和 87.15%，在阴离子类脂体（Tween 61/CHL/DP 摩尔比为 1:1:0.05）中分别为 50.13%、90.88%和 44.31%。在中性、阴离子和阳离子类脂体中，BSA、BCT 和胰岛素的最高包封效率分别为 72.94%、90.88%和 87.15%。本研究结果表明，对于药物应用，有合适的类脂体配方可以包封具有不同电荷和极性的肽类。
