Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing 100038, China.
Biomed Res Int. 2021 Jul 3;2021:9968602. doi: 10.1155/2021/9968602. eCollection 2021.
Chemotherapeutic drugs cause severe toxicities if administered unprotected, without proper targeting, and controlled release. In this study, we developed topotecan- (TPT-) loaded solid lipid nanoparticles (SLNs) for their chemotherapeutic effect against colorectal cancer. The TPT-SLNs were further incorporated into a thermoresponsive hydrogel system (TRHS) (TPT-SLNs-TRHS) to ensure control release and reduce toxicity of the drug. Microemulsion technique and cold method were, respectively, used to develop TPT-SLNs and TPT-SLNs-TRHS. Particle size, polydispersive index (PDI), and incorporation efficiency (IE) of the TPT-SLNs were determined. Similarly, gelation time, gel strength, and bioadhesive force studies of the TPT-SLNs-TRHS were performed. Additionally, release and pharmacokinetic and antitumour evaluations of the formulation were done.
TPT-SLNs have uniformly distributed particles with mean size in nanorange (174 nm) and IE of ~90%. TPT-SLNs-TRHS demonstrated suitable gelation properties upon administration into the rat's rectum. Moreover, drug release was exhibited in a control manner over an extended period of time for the incorporated TPT. Pharmacokinetic studies showed enhanced bioavailability of the TPT with improved plasma concentration and AUC. Further, it showed significantly enhanced antitumour effect in tumour-bearing mice as compared to the test formulations.
It can be concluded that SLNs incorporated in TRHS could be a potential source of the antitumour drug delivery with better control of the drug release and no toxicity.
如果没有适当的靶向和控制释放，未经保护地施用化疗药物会导致严重的毒性。在这项研究中，我们开发了载有拓扑替康（TPT）的固体脂质纳米粒（SLNs），用于治疗结直肠癌的化疗作用。进一步将 TPT-SLNs 纳入热敏水凝胶系统（TRHS）（TPT-SLNs-TRHS）中，以确保药物的控制释放和降低毒性。分别采用微乳液技术和冷法制备 TPT-SLNs 和 TPT-SLNs-TRHS。测定 TPT-SLNs 的粒径、多分散指数（PDI）和包封效率（IE）。同样，对 TPT-SLNs-TRHS 进行了凝胶时间、凝胶强度和生物粘附力研究。此外，还进行了释放、药代动力学和抗肿瘤评价。
TPT-SLNs 具有均匀分布的颗粒，平均粒径在纳米范围内（174nm），IE 约为 90%。TPT-SLNs-TRHS 在注入大鼠直肠后表现出合适的凝胶化特性。此外，包封的 TPT 能够在较长时间内以控制方式释放药物。药代动力学研究表明，与测试制剂相比，TPT 的生物利用度得到了提高，血浆浓度和 AUC 得到了改善。此外，它在荷瘤小鼠中表现出显著增强的抗肿瘤作用。
可以得出结论，纳入 TRHS 的 SLNs 可能是一种具有更好的药物释放控制和无毒性的抗肿瘤药物递送的潜在来源。
Zotero 插件
