Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Department of Pharmaceutics, PCTE Institute of Pharmacy, PTU, Ludhiana, Punjab, India.
AAPS PharmSciTech. 2021 Feb 3;22(2):64. doi: 10.1208/s12249-021-01922-1.
The aim of the study was to prepare 5-fluorouracil (5-FU)-loaded biogenic gold nanoparticles with pluronic-based coating (PFGNPs), their optimization (full factorial predicted OBPN-1) and in vitro-ex vivo evaluation. Several formulations were prepared, selected for optimization using Design Expert®, and compared for morphology, 5-FU release kinetics, compatibility, cell line toxicity, in vitro hemocompatibility, and ex vivo intestinal permeation across the rat duodenum, jejunum, and ileum. The pluronic-coated 5-FU-carrying GNPs were spherical, 29.11-178.21 nm in diameter, with a polydispersity index (PDI) range of 0.191-292, and a zeta potential (ZP) range of 11.19-29.21 (-mV). The optimized OBPN-1 (desirability = 0.95) demonstrated optimum size (175.1 nm), %DL as 73.8%, ZP as 21.7 mV, % drug release (DR) as 75.7%, and greater cytotoxicity (viability ~ 8.9%) against the colon cancer cell lines than 5-FU solution (~ 24.91%), and less hemocompatibility. Moreover, OBPN-1 exhibited 4.5-fold permeation across the rat jejunum compared with 5-FU solution. Thus, the PFGNPs exhibit high DL capacity, sustained delivery, hemocompatibility, improved efficacy, and enhanced permeation profiles compared with 5-FU solution and several other NPs preparations suggesting it is a promising formulation for effective colon cancer control with reduced side effects.
本研究旨在制备载有 5-氟尿嘧啶(5-FU)的生物衍生金纳米粒子,并用基于普朗尼克的涂层(PFGNPs)对其进行包载,对其进行优化(采用完全析因预测最佳点 OBPN-1)并进行体外-体外评估。制备了几种制剂,使用 Design Expert®选择优化,比较了形态、5-FU 释放动力学、相容性、细胞系毒性、体外血液相容性以及在大鼠十二指肠、空肠和回肠中的体外肠道渗透。载有 5-FU 的 PFGNPs 呈球形,直径为 29.11-178.21nm,多分散指数(PDI)范围为 0.191-292,zeta 电位(ZP)范围为 11.19-29.21(-mV)。优化后的 OBPN-1(理想度=0.95)显示出最佳尺寸(175.1nm)、载药量(DL)为 73.8%、ZP 为 21.7mV、药物释放(DR)为 75.7%、对结肠癌细胞系的细胞毒性(活力8.9%)大于 5-FU 溶液(24.91%),血液相容性较低。此外,与 5-FU 溶液相比,OBPN-1 显示出 4.5 倍的大鼠空肠渗透性。因此,与 5-FU 溶液和其他几种 NPs 制剂相比,PFGNPs 表现出高载药量、持续释放、血液相容性、更好的疗效和增强的渗透特性,提示其是一种有前途的制剂,可有效控制结肠癌并减少副作用。