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

• Published in: Biomolecules (Basel, Switzerland) Vol. 11; no. 1; p. 109
• Main Authors: A Attia, Mohammed, Enan, Eman T, Hashish, Abdullah A, M H El-Kannishy, Sherif, Gardouh, Ahmed R, K Tawfik, Mona, Faisal, Salwa, El-Mistekawy, Amr, Salama, Ayman, Alomar, Suliman Y, H Eltrawy, Amira, Yagub Aloyouni, Sheka, Zaitone, Sawsan A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-01-2021; MDPI
• Subjects: 1,2-Dimethylhydrazine; 5-Fluorouracil; 5-flurouracil; Apoptosis; Cancer therapies; Caspase-3; Chemotherapy; Colon cancer; Colorectal cancer; Drug delivery systems; Drug development; Drug dosages; Dysplasia; Efficiency; experimental colon dysplasia; Glycolic acid; Lecithin; Lipids; mouse; Mucosa; Nanoparticles; Oral administration; p53 Protein; Particle size; Pharmacokinetics; PLGA-lecithin; Polylactide-co-glycolide; polymeric lipid hybrid nanoparticles; Polymers; Surfactants; Variables; Italy; Sweden; United Kingdom > UK; United States > US; Germany; mouse; apoptosis; experimental colon dysplasia; PLGA-lecithin; 5-flurouracil; polymeric lipid hybrid nanoparticles
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11010109

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.