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.

中文翻译：

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5-氟尿嘧啶聚合物杂合PLGA-卵磷脂纳米颗粒对小鼠结肠不典型增生模型的化学预防作用及对p53细胞凋亡的影响。

5-氟尿嘧啶（5FU）的使用与多方面的挑战和不良的药代动力学有关。基于聚（乳酸-乙醇酸）-脂质杂化纳米颗粒（PLNs）的治疗方法已作为多种药物的有效载体而受到关注。这项研究评估了5FU负载的PLN对1,2-二甲基肼（Di-MH）提示小鼠结肠不典型增生的体内化疗和抗增殖功效，与游离5FU相比。制备了5FU PLN。将瑞士白化病雄性小鼠分为六个实验组。第一组：盐水组。所有其他组每周注射Di-MH [20 mg / kg，sc]。第2组：Di-MH诱导的结肠发育不良对照组。第3和第4组：Di-MH +游离5FU治疗组[2.5和5 mg / kg]。第5和第6组：Di-MH + 5FU-PLNs治疗组[2.5和5 mg / kg]。每周两次免费口服5FU和5FU-PLNs。5FU-PLNs与游离5FU相比具有更高的细胞保护作用，这表现为更低的粘膜组织病理学评分和Ki-67免疫阳性增殖核数目的减少。此外，结肠标本中p53和caspase 3基因显着上调。我们的研究结果支持利用PLNs技术改善5FU在治疗结肠癌中的化学预防作用的有效性。