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基于 Pluronic 共包覆的生物源性金纳米粒经结肠递释 5-氟尿嘧啶:体外与离体研究。

Pluronic-Coated Biogenic Gold Nanoparticles for Colon Delivery of 5-Fluorouracil: In vitro and Ex vivo Studies.

机构信息

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.

Department of Pharmaceutics, PCTE Institute of Pharmacy, PTU, Ludhiana, Punjab, India.

出版信息

AAPS PharmSciTech. 2021 Feb 3;22(2):64. doi: 10.1208/s12249-021-01922-1.

Abstract

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.

摘要

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。

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