Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran.
Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Pharm Res. 2017 Dec;34(12):2798-2808. doi: 10.1007/s11095-017-2260-x. Epub 2017 Nov 6.
Letrozole as a steroidal anticancer drug with hydrophobic nature is usually administrated by oral route for patient treatment and the injectable formulation for this drug has not still been reported. In this study, a new letrozole incorporated folate-conjugated polymer - lipid hybrid nanoparticles - is introduced for cancer treatment.
Nanoparticles were fabricated via modified oil in water ionic gelation method using optimization parameters and then were coupled to folic acid using carbodiimide activation. The physicochemical characterization in vitro drug release, cytotoxicity, and then ex vivo study of obtained carrier was investigated.
Both thermal and crystallography studies proved the amorphous loading of drug in the nanocarrier. The cytotoxicity investigation with an average IC value of 79 ± 2.40 nM proved the efficiency of the coupled folic acid carrier for the intracellular uptake of letrozole on the breast cancer line. Ex vivo, the study proved the positive effect of the letrozole entrapment on the drug bioavailability.
The obtained targeted nanocarrier could overcome the limitations associated with the LTZ as a potent non-steroidal drug. Both the entrapment and therapeutic efficiency of letrozole in the amphiphilic carrier were increased using the lipid nanoparticles and the surface modification, respectively.
来曲唑是一种具有疏水性的甾体抗癌药物，通常通过口服途径用于患者治疗，而该药物的注射制剂尚未报道。在这项研究中，引入了一种新的载有叶酸的聚合物-脂质杂化纳米粒子来治疗癌症。
通过改良的油包水离子凝胶化法，使用优化参数制备纳米粒子，然后使用碳二亚胺活化将其与叶酸偶联。对获得的载体进行了体外药物释放、细胞毒性等理化性质的表征，然后进行了体外研究。
热分析和结晶学研究均证明了药物在纳米载体中的无定形负载。细胞毒性研究表明，平均 IC 值为 79±2.40nM，证明了偶联叶酸载体对乳腺癌细胞系来曲唑细胞内摄取的有效性。体外研究证明了来曲唑包封对药物生物利用度的积极影响。
所获得的靶向纳米载体可以克服来曲唑作为一种强效非甾体药物所带来的限制。通过脂质纳米粒子和表面修饰，分别提高了来曲唑在两亲性载体中的包封率和治疗效率。
