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

被引：8

作者：

A. Attia, Mohammed ^{[1
,2
]}

Enan, Eman T. ^{[3
]}

Hashish, Abdullah A. ^{[4
,5
]}

M. H. El-kannishy, Sherif ^{[6
,7
]}

Gardouh, Ahmed R. ^{[8
,9
]}

K. Tawfik, Mona ^{[10
]}

Faisal, Salwa ^{[11
]}

El-Mistekawy, Amr ^{[12
]}

Salama, Ayman ^{[13
,14
]}

Alomar, Suliman Y. ^{[15
]}

H. Eltrawy, Amira ^{[16
]}

Yagub Aloyouni, Sheka ^{[17
]}

Zaitone, Sawsan A. ^{[7
,18
]}

机构：

[1] Mansoura Univ, Fac Med, Dept Clin Pharmacol, Mansoura 35516, Egypt

[2] AlMaarefa Univ, Dept Pharmacol, Coll Med, Riyadh 11597, Saudi Arabia

[3] Mansoura Univ, Dept Pathol, Fac Med, Mansoura 35516, Egypt

[4] Suez Canal Univ, Dept Clin Pathol, Fac Med, Ismailia 41522, Egypt

[5] Univ Bisha, Coll Med, Basic Med Sci Dept, Bisha 61922, Saudi Arabia

[6] Mansoura Univ, Mansoura Hosp, Dept Toxicol, Fac Med, Mansoura 35516, Egypt

[7] Univ Tabuk, Dept Pharmacol & Toxicol, Fac Pharm, Tabuk 71491, Saudi Arabia

[8] Suez Canal Univ, Dept Pharmaceut & Ind Pharm, Fac Pharm, Ismailia 41522, Egypt

[9] Jadara Univ, Fac Pharm, Dept Pharm, Irbid 21110, Jordan

[10] Suez Canal Univ, Fac Med, Dept Clin Pharmacol, Ismailia 41522, Egypt

[11] Suez Canal Univ, Fac Med, Dept Biochem & Mol Biol, Ismailia 41522, Egypt

[12] Al Azhar Univ, Fac Med, Gastroenterol Div, Dept Internal Med, Cairo 11651, Egypt

[13] Univ Tabuk, Fac Pharm, Dept Pharmaceut, Tabuk 71491, Saudi Arabia

[14] Al Azhar Univ, Fac Pharm Boys, Dept Pharmaceut & Ind Pharm, Cairo 11751, Egypt

[15] King Saud Univ, Dept Zool, Coll Sci, Doping Res Chair, Riyadh 11495, Saudi Arabia

[16] Alexandria Univ, Dept Anat & Embryol, Fac Med, Alexandria 22785, Egypt

[17] Princess Nourah Bint Abdulrahman Univ, Hlth Sci Res Ctr, Riyadh 84428, Saudi Arabia

[18] Suez Canal Univ, Fac Pharm, Dept Pharmacol & Toxicol, Ismailia 41522, Egypt

来源：

BIOMOLECULES | 2021年 / 11卷 / 01期

关键词：

apoptosis; 5-flurouracil; experimental colon dysplasia; mouse; polymeric lipid hybrid nanoparticles; PLGA-lecithin;

D O I：

10.3390/biom11010109

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1 / 20

页数：20

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