乳铁蛋白修饰的烟酰胺单核苷酸脂质体的制备与评价OA
Preparation and Evaluation of Lactoferrin-Modified Niacinamide Mononucleotide Liposomes
为改善烟酰胺单核苷酸(NMN)的脑靶向性并增强其血脑屏障透过性,采用复乳法结合功能化修饰策略构建并制备乳铁蛋白修饰的烟酰胺单核苷酸脂质体(NMN-Lip-Lf).首先通过单因素实验及Box-Behnken响应面法优化脂质体处方与工艺参数:确定膜脂比1∶9.5、NMN药液质量浓度4 mg/mL、DSPE-PEG2000 物质的量占比 3%;优化超声乳化条件(内水相/有机相体积比1∶4.3,内水相/外水相体积比 1∶9,超声功率 200 W,两次乳化时间分别为 4.5、1 min,减压蒸发参数(32℃、10 min)).进一步通过酯化反应将DSPE-PEG2000-COOH替换部分DSPE-PEG2000,并与乳铁蛋白偶联制备功能化脂质体.表征结果显示,NMN-Lip-Lf 粒径(147.40±5.49)nm,PDI 0.26±0.05,Zeta 电位-(8.87±0.41)mV,包封率和载药量分别为(25.11±1.35)%、(5.02±0.27)%.胶体稳定性良好,体外释放呈现明显的药物缓释特性.体外血脑屏障模型实验结果显示,与原料药(NMN)和未修饰脂质体(NMN-Lip)相比,NMN-Lip-Lf的血脑屏障透过率分别提升为它们的 6.2倍、4.7 倍.此结果为NMN中枢神经系统靶向递送系统的开发应用提供了新策略.
In order to improve the brain targeting of nicotinamide mononucleotide(NMN)and enhance its blood-brain barrier permeability,lactoferrin-modified nicotinamide mononucleotide liposomes(NMN-Lip-Lf)were con-structed and prepared using a multi-emulsion method combined with a functional modification strategy.First,the formulation and process parameters of the liposome were optimized using single factor experiment and Box-Behnken response surface method.The optional conditions were as follows:membrane lipid ratio of 1∶9.5,lipid concentra-tion of 4 mg/mL,and a molar ratio of DPE-PEG2000 was 3%.The ultrasonic emulsification conditions were opti-mized:an internal water phase/organic phase volume ratio 1∶4.3,an internal water phase/external water phase volume ratio 1∶9,ultrasonic power 200 W,two emulsification durations of 4.5 min and 1 min,respectively,and vacuum evaporation parameters(32℃for 10 min).Further,DSPE-PEG2000-COOH was partially replaced with DSPE-PEG2000 via an esterification reaction and coupled with lactoferrin to prepare functionalized liposomes.The results showed that the particle size of NMN-Lip-Lf was(147.40±5.49)nm,the PDI was 0.26±0.05,the Zeta potential was-(8.87±0.41)mV,and the encapsulation efficiency and drug loading were(25.11±1.35)%and(5.02±0.27)%,respectively.The colloidal dispersion exhibited good stability,and the in vitro release study showed a slow-release profile.The results of the in vitro blood-brain barrier model experiment showed that the blood-brain barrier permeability of NMN-LiP-LF was 6.2-fold and 4.7-fold of original drug(NMN)and unmodified liposome(NMN-Lip)respectively.These results provide a new strategy for the development and application of NMN targeted delivery systems in the central nervous system.
ZHAO Fengdong;PING Songyuge;JIANG Yuanyuan;WU Kaihan;LIN Yuxian;FAN Yutong;XU Hui
School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,ChinaSchool of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,ChinaSchool of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,ChinaSchool of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,ChinaSchool of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,ChinaSchool of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,ChinaSchool of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,China
医药卫生
烟酰胺单核苷酸乳铁蛋白脂质体复乳法Box-Behnken响应面法血脑屏障
nicotinamide mononucleotidelactoferrinliposomedouble emulsion methodBox-Behnken response surface methodblood-brain barrier
《烟台大学学报（自然科学与工程版）》 2026 (1)
42-49,8
浙江省"尖兵领雁"研发攻关计划项目(2022C03145)烟台大学实验室开放基金项目(2024-2025学年).
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