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- Title
Chemopreventive Effect of 5-Flurouracil Polymeric Hybrid PLGA-Lecithin Nanoparticles against Colon Dysplasia Model in Mice and Impact on p53 Apoptosis.
- 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.
- 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.
- Subjects
COLON (Anatomy); NANOPARTICLES; APOPTOSIS; DRUG carriers; FLUOROURACIL; NANOMEDICINE; DYSPLASIA
- Publication
Biomolecules (2218-273X), 2021, Vol 11, Issue 1, p109
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom11010109