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

• Main Authors: Mohammed A. Attia, Eman T. Enan, Abdullah A. Hashish, Sherif M. H. El-kannishy, Ahmed R. Gardouh, Mona K. Tawfik, Salwa Faisal, Amr El-Mistekawy, Ayman Salama, Suliman Y. Alomar, Amira H. Eltrawy, Sheka Yagub Aloyouni, Sawsan A. Zaitone
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Biomolecules
• Subjects: apoptosis; 5-flurouracil; experimental colon dysplasia; mouse; polymeric lipid hybrid nanoparticles; PLGA-lecithin
• Online Access: https://www.mdpi.com/2218-273X/11/1/109

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.