Department of Gastroenterology, Binzhou Central Hospital, Binzhou, Shandong Province, China.
Department of Gastrointestinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shangdong, China.
Biotechnol Appl Biochem. 2022 Oct;69(5):2205-2221. doi: 10.1002/bab.2279. Epub 2021 Nov 25.
The present research work describes development of dual drug-loaded lipid-polymer hybrid nanoparticles (LPHNPs) of anticancer therapeutics for the management of colon cancer. The epidermal growth factor (EGF)-functionalized LPHNPs coloaded with 5-fluorouracil (FU) and sulforaphane (SFN) were prepared by one-step nanoprecipitation method. Box-Behnken design was applied for optimizing the material attributes and process parameters. The optimized LPHNPs revealed particle size 198 nm, polydispersity index 0.3, zeta potential -25.3 mV, and drug loading efficiency 19-20.3% for 5-FU and SFN, respectively. EGF functionalization on LPHNPs was confirmed from positive magnitude of zeta potential to 21.3 mV as compared with the plain LPHNPs. In vitro drug release performance indicated sustained and non-Fickian mechanism release nature of the drugs from LPHNPs. Anticancer activity evaluation in HCT-15 colon cancer cells showed significant reduction (p < 0.001) in the cell growth and cytotoxicity of the investigated drugs from various treatments in the order: EGF-functionalized LPHNPs > plain LPHNPs > free drug suspensions. Overall, the research work corroborated improved treatment efficacy of EGF-functionalized LPHNPs for delivering chemotherapeutic agents for the management of colon carcinoma.
本研究工作描述了用于结肠癌治疗的载双药物的脂质-聚合物杂化纳米颗粒（LPHNPs）的开发。通过一步法纳米沉淀法制备表皮生长因子（EGF）功能化的共载有 5-氟尿嘧啶（FU）和萝卜硫素（SFN）的 LPHNPs。采用 Box-Behnken 设计对材料属性和工艺参数进行优化。优化后的 LPHNPs 显示粒径为 198nm，多分散指数为 0.3，Zeta 电位为-25.3mV，5-FU 和 SFN 的载药效率分别为 19-20.3%。与普通 LPHNPs 相比，EGF 功能化的 LPHNPs 的 Zeta 电位为正 21.3mV，证实了 LPHNPs 的 EGF 功能化。体外药物释放性能表明，药物从 LPHNPs 中以持续和非菲克扩散机制释放。在 HCT-15 结肠癌细胞中的抗癌活性评估表明，在各种处理中，用 EGF 功能化 LPHNPs 处理的细胞生长和细胞毒性显著降低（p<0.001），其顺序为：EGF 功能化 LPHNPs>普通 LPHNPs>游离药物混悬液。总的来说，这项研究工作证实了 EGF 功能化 LPHNPs 用于递送化疗药物治疗结肠癌的疗效得到了改善。
