Antitumor activity and targeting p53-PUMA mRNA expression by 5-flurouracil PLGA-lipid polymeric nanoparticles in mouse mammary carcinomas: comparison to free 5-flurouracil.

Autor:	Alsharif ST; PharmD program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia., Gardouh AM; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Jadara University, Irbid, Jordan., Mandour MF; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt., Alaqais ZM; PharmD program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia., Alharbi LK; PharmD program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia., Almarwani MJ; PharmD program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia., Mokhtar HI; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sinai University-Kantara Branch, Ismailia, Egypt., Hisham FA; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Abdellah MM; Department of Pathology, Faculty of Medicine, Galala University, Suez, Egypt.; Department of Pathology, Faculty of Medicine, Fayoum University, Fayoum, Egypt., Mohamed GM; Nutrition and Food Science Department, College of Home Economics, Tabuk University, Tabuk, Saudi Arabia., Shorog EM; Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia., Almaeen AH; Pathology Department, College of Medicine, Jouf University, Jouf, Saudi Arabia., Atteia HH; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt., Zaitone SA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Jazyk:	angličtina
Zdroj:	Toxicology mechanisms and methods [Toxicol Mech Methods] 2024 May; Vol. 34 (4), pp. 385-397. Date of Electronic Publication: 2024 Jan 08.
DOI:	10.1080/15376516.2023.2294083
Abstrakt:	Polymeric poly (lactic-co-glycolic acid) (PLGA)-lipid hybrid nanoparticles (PNPs)-based therapy are powerful carriers for various therapeutic agents. This study was conducted to evaluate the chemotherapeutic potential of free 5-flurouracil (5FU) and synthetized 5FU-PNPs and impact on p53-dependent apoptosis in mammary carcinomas (MCs) grown in mice. Breast cancer cells were injected in Swiss albino female mice and 2 bilateral masses of MC were confirmed after one week. Mice were distributed to five experimental groups; Group 1: MC control group. Groups 2 and 3: MC + free 5FU [5 or 10 mg per kg] groups. Groups 4 and 5: synthetized MC+ 5FU-PNPs [5 or 10 mg per kg] groups. Medications were administered orally, twice weekly for 3 weeks. Then, tumors were dissected, and sections were stained with hematoxylin-eosin (HE) while the other MC was used for measuring of cell death and inflammatory markers. Treatment with 5FU-PNPs suppressed the MC masses and pathologic scores based on HE-staining. Similarly, greater proapoptotic activity was recorded in 5FU-PNPs groups compared to free 5FU groups as shown by significant upregulation in tumoral p53 immunostaining. The current results encourage the utility of PNPs for improving the antitumor effect of 5FU. The chemotherapeutic potential was mediated through enhancement of tumoral p53-mediated p53 up-regulated modulator of apoptosis (PUMA) genes. Additional studies are warranted for testing the antitumor activity of this preparation in other mouse models of breast cancer.
Databáze:	MEDLINE
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