Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Punjab, Pakistan.
Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Punjab, Pakistan.
Life Sci. 2021 Nov 1;284:119909. doi: 10.1016/j.lfs.2021.119909. Epub 2021 Aug 25.
The present study aimed to develop and characterize poly (ɛ-caprolactone) (PCL) based lipid polymer hybrid nanoparticles for sustained delivery and in-vitro anti-cancer activity in MCF-7 and HeLa cells cancer cell line.
The nanoprecipitation method was used for the development of 5-fluorouracil loaded lipid polymer hybrid nanoparticles (LPHNPs). The developed LPHNPs were characterized for physicochemical characteristics and the anti-cancer effect was evaluated in MCF-7 and HeLa cells.
Six formulations having fixed amount of drug and varied lipid, polymer and emulsifier concentrations were prepared. The particle size was in the range of 174 ± 4 to 267 ± 2.65 nm, entrapment efficiency (92.87 ± 0.594 to 94.13 ± 0.772%), negative zeta potential, optimum polydispersity index and spherical shape. FTIR analysis shows no chemical interaction among the formulation components, DSC analysis reveals the disappearance of 5-FU melting endotherm in the developed LPHNPs suggesting amorphization of 5-FU in the developed system, XRD analysis indicates successful encapsulation of the drug in the lipid polymer matrix. The in-vitro release shows a biphasic release pattern with an initial burst release followed by a sustained release profile for 72 h. The drug loaded LPHNPs exhibited a greater cytotoxic effect than 5-FU solution due to sustained release and increased cellular internalization. The acute toxicity study revealed the safety of the developed carrier system for potential delivery of chemotherapeutic agents.
The developed LPHNPs of 5-fluorouracil will provide the sustained release behavior of 5-fluorouracil to maximize the therapeutic efficacy and minimize the dose related toxicity.
本研究旨在开发和表征聚（ε-己内酯）（PCL）基脂质聚合物杂化纳米粒，用于 MCF-7 和 HeLa 细胞系的持续递药和体外抗癌活性。
采用纳米沉淀法制备 5-氟尿嘧啶负载的脂质聚合物杂化纳米粒（LPHNPs）。对所开发的 LPHNPs 进行理化特性表征，并在 MCF-7 和 HeLa 细胞中评估其抗癌作用。
制备了六种固定药物剂量、改变脂质、聚合物和乳化剂浓度的制剂。粒径在 174±4 至 267±2.65nm 之间，包封效率为 92.87±0.594 至 94.13±0.772%，负ζ电位、最佳多分散指数和球形。傅里叶变换红外光谱（FTIR）分析表明制剂成分之间没有化学相互作用，差示扫描量热法（DSC）分析表明开发的 LPHNPs 中 5-FU 的熔融吸热峰消失，表明 5-FU 在开发系统中呈无定形状态，X 射线衍射（XRD）分析表明药物成功包封在脂质聚合物基质中。体外释放呈现出双相释放模式，初始突释后持续释放 72 小时。载药 LPHNPs 表现出比 5-FU 溶液更大的细胞毒性作用，这是由于持续释放和增加细胞内化所致。急性毒性研究表明，所开发的载体系统用于潜在的化疗药物输送是安全的。
开发的 5-氟尿嘧啶 LPHNPs 将提供 5-氟尿嘧啶的持续释放行为，以最大限度地提高治疗效果并最小化剂量相关毒性。
