Abstract

Background5-Fluorouracil (5-FU) is one of the most classic chemotherapy drugs. Nanoparticle drug delivery vehicles offer superiority over target effect enhancement and abatement of side effects. Little is known however as to the specific effect of nanoparticle on peritoneal dissemination of colon cancer. The aim of this study is to prepare one NPs (nanoparticles) loaded with 5-FU and investigate the characteristic of NPs and the role of it in peritoneal metastasis nodules formation of human colon cancer.Methodology/Principal FindingsPrepared the NPs (nanoparticles) loaded with 5-FU (5-Fluorouracil) by PEG-PLGA with the method of double emulsion. Then evaluate the characteristics of the NPs by scanning electron microscopy, analyzing the particle diameter distribution and determining the loading efficiency. Detect the release features of NPs in vitro and in vivo. Nude mice with peritoneal metastases were treated with 5-FU solution or 5-FU-NPs through peritoneal cavity. Count the nodules on peritoneum and mesenterium and survey the size of them. We got NPs with average-diameter of 310 nm. In vitro release test shows NPs can release equably for 5 days with release rate of 99.2%. In vivo, NPs group can keep higher plasma concentration of 5-FU longer than it in solution group. The number of peritoneal dissemination nodule below 1 mm in 5-FU-sol group(17.3±3.5) and 5-FU-NP group(15.2±3.2) is less than control group(27.2±4.7)(P<0.05). The total number of nodules in 5-FU-NP group(28.7±4.2) is significantly smaller than in 5-FU-sol group(37.7±6.3) (P<0.05).Conclusions/SignificanceThe novel anti-tumor nanoparticles loaded with 5-FU by PEG-PLGA can release maintain 5 days and have inhibitory action to peritoneal dissemination of colon cancer in mice.

Highlights

  • Colorectal cancer is the third leading cause of cancer-related deaths worldwide

  • Peritoneal metastasis of colorectal cancer is common with incidence of about 13% which were reported in study on large sample previously [1].Peritoneal metastasis occurred in 7% of patients with colorectal cancer in the initial treatment and in 4%,19% patients after radical surgery [2].The prognosis of colorectal cancer peritoneal metastasis is poor whose median survival is only 5,9 months [3].The current systemic chemotherapy regimens based on 5-FU for colorectal cancer have not achieved satisfactory results, in the treatment of peritoneal dissemination [4]

  • Direct intraperitoneal administration may cause 5-FU absorbed into blood circulation rapidly result in the insufficient dose arrive at local nodule in peritoneal cavity

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Summary

Introduction

Colorectal cancer is the third leading cause of cancer-related deaths worldwide. Peritoneal metastasis of colorectal cancer is common with incidence of about 13% which were reported in study on large sample previously [1].Peritoneal metastasis occurred in 7% of patients with colorectal cancer in the initial treatment and in 4%,19% patients after radical surgery [2].The prognosis of colorectal cancer peritoneal metastasis is poor whose median survival is only 5,9 months [3].The current systemic chemotherapy regimens based on 5-FU for colorectal cancer have not achieved satisfactory results, in the treatment of peritoneal dissemination [4]. It is necessary to develop new strategies for the treatment of peritoneal dissemination in colorectal cancer to achieve better results. Nanoparticle, as a novel carrier for anti-tumor drugs, has been paid a close attention to by the medical field in early 1978 till [6]. Neovessels in tumor are more permeable for nanoparticles under 400–600 nm to pass, which can improve the target function and can lessen the side effects of anti-tumor drugs[11]. While,the intraperitoneal administration of nanoparticle antitumor agents for the treatment of colorectal cancer peritoneal dissemination has not been investigated extensively. We prepared the 5-FU nanoparticles with a novel technique firstly, and demonstrated anti-tumor nanoparticles can inhibit formation of peritoneal dissemination of colorectal cancer

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