siRNA-阳离子脂质体干粉吸入剂的制备与评价OA
Preparation and Evaluation of a Cationic Liposome/siRNA Dry Powder for Inhalation
针对KRAS靶向药物开发中传统siRNA系统递送效率低的问题,构建了基于阳离子脂质体的siRNA干粉吸入剂(siRNA-LP-DPI),通过肺部递送途径提升药物靶向性.通过系统评估冻干制剂的表观形态、粒径分布、Zeta电位及再分散性等关键参数,对保护剂种类、预冻温度等工艺条件进行优化.以5%甘露醇为冻干保护剂,预冻温度-80℃,干燥后获得白色蓬松粉末状si RNA-LP-DPI,其再分散性好,略有引湿性,复溶后的平均粒径为(98.66±2.61)nm,Zeta电位为(4.98±0.45)mV,展现出良好的物理稳定性.体外细胞毒性实验结果表明,与游离siRNA溶液对照组相比,siRNA-LP和siRNA-LP-DPI均能显著降低A549 肿瘤细胞的活力;且冻干后对siRNA的生物活性无明显影响.细胞摄取实验进一步证实,siRNA-LP-DPI显著提高了A549 细胞对siRNA的摄取效率.本研究为开发新型肺部靶向抗肿瘤疗法提供了有效的技术策略,有望为非小细胞肺癌患者提供一种高效、安全的治疗选择.
To address the low delivery efficency of conventional siRNA systems in KRAS-targeted drug develop-ment,we developed a cationic liposome-based siRNA dry powder inhaler(siRNA-LP-DPI)to enhance pulmonary drug targeting efficiency.Key parameters—including apparent morphology,particle size distribution,Zeta poten-tial,and redispersibility—were systematically evaluated to optimize process conditions,such as cryoprotectant type and pre-freezing temperature.Using 5%mannitol as the cryoprotectant and a pre-freezing temperature of-80℃,we obtained a white,fluffy siRNA-LP-DPI powder after drying.The optimized formulation exhibited excellent redis-persibility and minimal hygroscopicity,with a redispersed particle size of(98.66±2.61)nm and a Zeta potential of(4.98±0.45)mV,demonstrating favorable physical stability.In vitro cytotoxicity assays revealed that both siRNA-LP and siRNA-LP-DPI significantly reduced A549 tumor cell viability compared to free siRNA controls,with no loss of siRNA bioactivity after lyophilization.Cellular uptake studies further confirmed that siRNA-LP-DPI substantially enhanced siRNA uptake efficiency in A549 cells.This study provides an effective lung-targeted antitu-mor strategy,offering a promising and safe therapeutic approach for non-small cell lung cancer patients.
LI Xiao;LU Yanxiu;LU Kerui;YU Xiaoyu;LIU Sha
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,China
医药卫生
KRASsiRNA阳离子脂质体冷冻干燥干粉吸入剂非小细胞肺癌
KRASsiRNAcationic liposomefreeze dryingdry powder inhalernon-small cell lung cancer
《烟台大学学报（自然科学与工程版）》 2026 (1)
32-41,10
山东省自然科学基金资助项目(ZR2023MH318).
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