乳铁蛋白介导的肺靶向纳米脂质载体的研究进展

Research Progress on Lactoferrin-mediated Lung Targeting Nanostructured Lipid Carriers

纳米脂质载体属纳米给药体系,是在固体脂质纳米粒基础上发展起来的新型靶向给药系统,以生物相容性好的固态和液态脂质混合作为载体材料,将药物包裹于类脂核中,具有胶体载体如脂质体和纳米乳的优势,可用作抗肿瘤药物的靶向载体,同时,相比而言,纳米脂质载体雾化稳定性更好,在气道中具有良好的耐受性和理想的肺沉积率,适用于雾化吸入给药,该给药方式可使药物直达病灶,雾滴长时间滞留在肿瘤部位,发挥长效作用。为进一步提高药物的生物利用度、增强肺癌靶向性,可用乳铁蛋白对纳米脂质载体进行表面修饰。乳铁蛋白属转铁蛋白家族,正常肺组织中转铁蛋白受体呈阴性或低表达,而在非小细胞肺癌中转铁蛋白的阳性表达率远远高于正常肺组织,存在过度表达现象,可利用乳铁蛋白作为配体修饰纳米脂质载体,通过转铁蛋白介导的方式增加药物在肺癌细胞内的富集,受体介导的内吞可以进一步促进负载药物的纳米脂质载体的细胞摄取。

Nanostructured lipid carrier is a nano drug delivery system,which is a new targeted drug delivery system developed on the basis of solid lipid nanoparticles.It takes the mixture of solid and liquid lipids with good biocompatibility as the carrier material,and wraps the drug in the lipid core.It has the advantages of colloidal carriers such as liposomes and nano emulsion,and can be used as the targeted carrier of anti-tumor drugs.At the same time,compared with them,nanostructured lipid carrier has better atomization stability.It has good tolerance and ideal lung deposition rate in the airway,and is suitable for aerosol inhalation administration.This administration method can make the drug reach the focus directly,and the droplets stay at the tumor site for a long time to play a long-term role.In order to further improve the bioavailability of drugs and enhance the targeting of lung cancer,lactoferrin can be used to modify the surface of nanostructured lipid carriers.Lactoferrin belongs to the transferrin family.The transferrin receptor is negative or low expressed in normal lung tissue.However,the positive expression rate of transferrin in non-small cell lung cancer is much higher than that in normal lung tissue.There is an overexpression phenomenon.Lactoferrin can be used as a ligand to modify nanostructured lipid carriers to increase the concentration of drugs in lung cancer cells through transferrin mediated methods,receptor mediated endocytosis can further promote the cellular uptake of drug loaded nanostructured lipid carriers.