Chemopreventive Effect of 5-Flurouracil Polymeric Hybrid PLGA-Lecithin Nanoparticles against Colon Dysplasia Model in Mice and Impact on p53 Apoptosis.

Mohammed A Attia,Ayman Salama,Mona K Tawfik,Salwa Faisal,Sherif M H El-Kannishy,Ahmed R Gardouh,Sawsan A Zaitone,Sheka Yagub Aloyouni,Amira H Eltrawy,Abdullah A Hashish,Amr El-Mistekawy,Eman T Enan,Suliman Y Alomar

doi:10.3390/biom11010109

Abstract

The use of 5-fluorouracil (5FU) is associated with multifaceted challenges and poor pharmacokinetics. Poly(lactic-co-glycolic acid)-lipid hybrid nanoparticles (PLNs)-based therapy has received attention as efficient carriers for a diversity of drugs. This study evaluated the in vivo chemotherapeutic and anti-proliferative efficacy of 5FU-loaded PLNs against 1,2-dimethylhydrazine (Di-MH) prompted colon dysplasia in mice compared to free 5FU. 5FU PLNs were prepared. Male Swiss albino mice were distributed to six experimental groups. Group 1: Saline group. All the other groups were injected weekly with Di-MH [20 mg/kg, s.c.]. Group 2: Di-MH induced colon dysplasia control group. Groups 3 and 4: Di-MH + free 5FU treated group [2.5 and 5 mg/kg]. Groups 5 and 6: Di-MH + 5FU-PLNs treated group [2.5 and 5 mg/kg]. Free 5FU and 5FU-PLNs doses were administered orally, twice weekly. Treatment with 5FU-PLNs induced a higher cytoprotective effect compared to free 5FU as indicated by lower mucosal histopathologic score and reduction in number of Ki-67 immunpositive proliferating nuclei. Additionally, there was significant upregulation of p53 and caspase 3 genes in colon specimens. Our results support the validity of utilizing the PLNs technique to improve the chemopreventive action of 5FU in treating colon cancer.

Highlights

Colorectal cancer is the most common cancer affecting the digestive tract and is a main leading cause of death worldwide [1]
Fifteen experimental runs of Poly(lactic-co-glycolic acid)-lipid hybrid nanoparticles (PLNs) prepared by the polymer, lipid, and surfactant
A correlation between the different factors and formulation was Fifteen experimental runs of PLNs prepared by the polymer, lipi established using the quadratic polynomial generated using the Box–Behnken design using

Summary

Introduction

Colorectal cancer is the most common cancer affecting the digestive tract and is a main leading cause of death worldwide [1]. Characteristics of colorectal cancer involve uncontrolled cell proliferation and growth involving colonic crypt epithelial lining cells, beginning with hyperplasia and slowly evolving into invasive carcinoma [2]. Several animal models of colon cancer have been developed in order to explore its molecular pathogenesis and to investigate the role of various potential preventive nutritional and pharmacologic agents [3]. Significant progress in chemotherapy for colorectal cancer has been made, in which. 5-fluorouracil (5FU) is still representing one of the cornerstones and most active anti-cancer drugs among them. Nowadays, delivering safe and efficient doses of drugs is an ultimate goal of modern cancer chemotherapy; these doses will target the disease sites and spare the normal tissues [7].

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