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Abstract：
Relationship between the stability of fat nano-emulsions and the incorporated drug at the molecular level are rarely known. Herein, fat nano-emulsions containing dihydropyridine drugs were prepared and the microstructure of their palisade layers were investigated.The prepared 1.0 mg/mL nimodipine nano-emulsion was found to contain 65.50% drug in the palisade layer. The increasing drug concentration led to a decrease-increase-decrease trend in centrifugal stability constant, particle size and proton nuclear magnetic resonance (1H NMR) signal intensity of the lecithin trimethyl ammonium group in the nimodipine and felodipine nano-emulsions. The 1H NMR spectra of test solutions including nano-emulsions suggest that increasing drugs penetrated into the palisade layer, resulting in the lecithin arrangement from loose to tight, and then from monolayer to bilayer. Nimodipine and felodipine nano-emulsions showed two valley values at concentrations of 0.15 and 0.75 mg/mL, and 0.30 and 0.90 mg/mL respectively, which indicated that the nano-emulsion has two more stable states corresponding to the tightly arranged mono- and bi-palisade layer. These two concentrations are positively correlated with lipophilicity of nimodipine and felodipine. Further, nimodipine liposomes were prepared to validate the effect of drugs on the arrangement of lecithin in the palisade layer. 1H NMR characterizations of the liposomes showed a similar profile to that of nano-emulsions. These results demonstrated that the increasing drug concentration could cause a rearrangement of lecithin in the palisade layer, thus affecting emulsion stability.
摘要：
脂肪纳米乳液的稳定性与掺入的药物在分子水平上的关系鲜为人知。在这里，制备了含二氢吡啶类药物的脂肪纳米乳液，并研究了其栅栏层的微观结构。发现制备的1.0mg/mL尼莫地平纳米乳剂在栅栏层中含有65.50%的药物。药物浓度的增加导致离心稳定常数的减少-增加-减少趋势,尼莫地平和非洛地平纳米乳剂中卵磷脂三甲基铵基团的粒径和质子核磁共振(1HNMR)信号强度。包括纳米乳液在内的测试溶液的1HNMR光谱表明，越来越多的药物渗透到栅栏层中，导致卵磷脂排列从松散到紧密，然后从单层到双层。尼莫地平和非洛地平纳米乳剂在浓度为0.15和0.75mg/mL时显示出两个谷值,分别为0.30和0.90mg/mL，这表明纳米乳液具有两种更稳定的状态，对应于紧密排列的单层和双层栅栏层。这两个浓度与尼莫地平和非洛地平的亲脂性呈正相关。Further,制备尼莫地平脂质体以验证药物对卵磷脂在栅栏层中排列的影响。脂质体的1HNMR表征显示与纳米乳液相似的曲线。这些结果表明，药物浓度的增加可能导致卵磷脂在栅栏层中的重排，从而影响乳液稳定性。
