纳米白藜芦醇脂质体的制备及分配系数测定

doi:10.3866/PKU.WHXB201905090

摘要/Abstract

摘要：

采用薄膜旋转蒸发-超声法制备了纳米白藜芦醇脂质体(RES-Lip)，并用透射电子显微镜(TEM)和动态光散射技术(DLS)对产物进行表征；测定了膜材比(卵磷脂与胆固醇质量比m_PC : m_Chol = 5 : 1，8 : 1，10 : 1，12 : 1)和药脂比(药物与卵磷脂质量比m_RES : m_PC = 1 : 25，1 : 40，1 : 50，1 : 60)对RES-Lip脂质体-水分配系数(P_lip/w)的影响，以及油-水分配系数(lgP_o/w)和脂质体-水分配系数(lgP_lip/w)随pH值的变化趋势，计算了RES-Lip中药物与磷脂双分子膜之间的吉布斯自由能。结果表明，实验中所制备的RES-Lip呈球形囊泡结构，粒径约为100 nm；当膜材比和药脂比分别为10 : 1和1 : 40时，lgP_lip/w最大，说明此时RES与磷脂膜间的综合作用力最大；RES-Lip的分配系数(lgP_o/w和lgP_lip/w)随体系pH的变化趋势相同，说明RES与磷脂膜的作用力中以疏水作用为主，氢键、静电作用为辅；RES-Lip中RES与脂质体膜之间的吉布斯自由能为−17.07 kJ∙mol⁻¹。

关键词: 白藜芦醇, 脂质体, 油-水分配系数, 脂质体-水分配系数, 吉布斯自由能

Abstract:

Resveratrol is a natural polyphenol and phytoalexin with anti-inflammatory, anti-oxidant, anti-cancer, and neuroprotective effects. However, resveratrol exhibits low solubility, light sensitivity, poor absorption by oral administration, and short cycle time, which greatly limit its applications in medicine and the food industry. To overcome these limitations, a nano-resveratrol liposome (RES-Lip) was prepared. As a drug carrier, liposomes have many advantages such as good targeting properties, low toxicity, biocompatibility, and long-term sustained release. In liposomal studies, the oil-water (n-octanol-water) partition coefficient (P_o/w) is often used to predict the encapsulation and drug loading efficiencies. This method focuses on the lipophilicity of the drug, reflecting its hydrophobic action while ignoring the biological properties of the biofilm. The liposome-water partition coefficient (P_lip/w) reflects the structure of the biofilms and its interaction with drugs governed by factors including hydrophobicity, electrostatic forces, and hydrogen bonding. Herein, RES-Lip was successfully prepared using a rotary-evaporated film-ultrasonication method and subsequent characterization by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The effects of the membrane to material ratio (lecithin to cholesterol mass ratio m_PC : m_Chol = 5 : 1, 8 : 1, 10 : 1, and 12 : 1) and drug to lipid ratio (drug to lecithin mass ratio m_RES : m_PC = 1 : 25, 1 : 40, 1 : 50, and 1 : 60) of nano-resveratrol liposomes on the liposome-water partition coefficient (P_lip/w) were determined. Changes in the oil-water partition coefficient (lgP_o/w) and liposome-water partition coefficient (lgP_lip/w) as a function of pH were also determined. In addition, the Gibbs free energy between the drug and phospholipid bilayer membrane in RES-Lip was calculated. The results showed that RES-Lip adopted a spherical vesicle structure with a particle size of approximately 100 nm. When the membrane to material ratio was 10 : 1 and the drug to lipid ratio was 1 : 40, lgP_lip/w was maximized, indicating that the combined forces between RES and the phospholipid membrane were the highest at these ratios. The trends of lgP_o/w and lgP_lip/w as a function of pH were the same, indicating that the main interaction force between RES and the phospholipid membrane was the hydrophobic effect with secondary interaction forces of hydrogen bonding and electrostatic interaction. The Gibbs free energy between the RES and liposome membrane in RES-Lip was determined to be −17.07 kJ·mol⁻¹.

Key words: Resveratrol, Liposome, Oil-water partition coefficient, Liposome-water partition coefficient, Gibbs free energy

MSC2000:

O642.1

张茹,元琳琳,孙凯玥,王珊,耿丽娜,张建军. 纳米白藜芦醇脂质体的制备及分配系数测定[J]. 物理化学学报, 2020, 36(6): 1905090.

Ru Zhang,Linlin Yuan,Kaiyue Sun,Shan Wang,Lina Geng,Jianjun Zhang. Preparation and Partition Coefficient Determination of Nano-Resveratrol Liposomes[J]. Acta Physico-Chimica Sinica, 2020, 36(6): 1905090.

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Liposome	X_b/(mg·mL^?1)	P_f/(mg·mL^?1)	T/K	Ψ/mV	ΔG/(kJ·mol^?1)
RES-Lip	0.2268	0.000232	298.15	?70.57	?17.07

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