| 刘雅雯1†
，郭思茗1†
，顾乐炎2
，关丽萍1*
，曹青日2*.D-sn-GPHEEDA的制备及其脂质纳米粒的评价[J].海南师范大学学报自科版,2025,38(1):22-28 |
| D-sn-GPHEEDA的制备及其脂质纳米粒的评价 |
| Preparation of D-sn-GPHEEDA and Evaluation of its Lipid Nanoparticles |
| |
| DOI：10.12051/j.issn.1674-4942.2025.01.004 |
| 中文关键词: D-sn-GPHEEDA 脂质纳米粒 siRNA 稳定性 细胞毒性 |
| 英文关键词: D-sn-GPHEEDA lipid nanoparticles siRNA stability cytotoxicity |
| 基金项目:福 建 省 药 物 新 靶 点 研 究 重 点 实 验 室 开 放 课 题（FJ-YW-2023KF04）；浙 江 省 公 益 技 术 应 用 研 究 计 划
（2017C33131）；江苏省精准诊疗药物创制工程研究中心（发改办高技〔2021〕1368号） |
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| 中文摘要: |
| 优化以二油酰基卵磷脂为原料的1，2-二油酰-sn-甘油-3-磷脂酰羟乙基乙二胺合成
工艺，并评价脂质纳米粒的理化特性、siRNA结合力、血清稳定性和细胞毒性。通过HPLC、LC-MS、
1
H-NMR、13C-NMR表征确证其结构，考察了酶的用量、反应时间、反应物用量、两相反应体系比对
1，2-二油酰-sn-甘油-3-磷脂酰羟乙基乙二胺合成的影响。结果表明，最佳反应条件为酶用量
150 IU、最佳反应时间72 h、二油酰基卵磷脂与乙二胺的投料比1∶15、乙酸乙酯与乙酸钠缓冲溶液
的体积比2∶1时，产率达68.72%。所得脂质纳米粒的粒径为（102.100 ± 2.495） nm，平均多分散指
数为0.183 ± 0.023，Zeta电位为+（28.90 ± 2.46） mV，外观呈圆形，稳定性良好；在N/P比为12∶1时
可与 siRNA 完全结合，可显著提高 siRNA 的血清稳定性；MTT 结果表明所合成磷脂及其 LNPs 对
293T细胞活力无显著影响。该研究为其他磷脂酰化合物的合成及纳米递送载体的应用提供参考。 |
| 英文摘要: |
| In this study, we optimized the synthesis process of D-sn-GPHEEDA from dioleoyllecithin, and evaluated the
physicochemical properties, siRNA binding ability, serum stability and cytotoxicity of lipid nanoparticles (LNPs). The struc⁃
ture of D-sn-GPHEEDA was characterized by MS, 1
H-NMR and 13C-NMR, and the effects of enzyme dosage, reaction
time, reactant dosage and two reaction systems on the synthesis of D-sn-GPHEEDA were evaluated. The results showed
that the optimal reaction conditions were as follows: the enzyme dosage was 150 IU, the reaction time was 72 h, the ratio of
dioleyllecithin to ethylenediamine was 1:15, the volume ratio of ethyl acetate to sodium acetate buffer solution was 2:1, and
the yield was 68.72%. The prepared LNPs had a spherical appearance and uniform size distribution, with the particle size
of (102.100 ± 2.495) nm, PDI of 0.183 ± 0.023, zeta potential of + (28.9 ± 2.46) mV, respectively. The LNPs had good sta⁃
bility and can completely bind to siRNA at N/P ratio of 12∶1 and significantly improve the serum stability of siRNA.Though the MTT assay, the synthesized phospholipid and LNPs showed no significant effects on the viability of 293T cells. This
study provides a basis for the synthesis of other phospholipid compounds and the application of LNP-based nanocarriers. |
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