ABSTRACT
This paper aims to develop folic acid-modified paclitaxel nanocrystals (PTX NC@FA) with good stability, high drug loading and tumor cell targeting for endoscopic injection for preoperative local chemotherapy of gastric cancer. PTX NC@FA was prepared by the "bottom-up" followed by ultrasonic to study its morphology, particle size, ζ-potential, drug loading, folic acid-modified phospholipid (FA-DSPE-PEG2000) content, crystalline characteristics, stability, in vitro release, cytotoxicity against human gastric cancer cell line SGC-7901, and anti-tumor effect in two different tumor sizes (tumor volume 100 mm3 or 300 mm3) after single peri-tumor injection in a murine subcutaneous SGC-7901 tumor model. Animal experiments were approved by the Experimental Animal Ethics Committee of the School of Pharmacy, Fudan University. The resulting PTX NC@FA was of short rod-like shape, average particle size 175.3 ± 2.5 nm (PDI 0.17 ± 0.02), ζ- potential -2.5 ± 0.2 mV, PTX loading (28.23 ± 0.74) % (w/w) and FA-DSPE-PEG2000 content (4.40 ± 0.60) % (w/w). The size of the PTX NC@FA remained unchanged for 4 days in phosphate buffer with or without serum. Cellular growth inhibition effect on SGC-7901 showed the superiority of PTX NC@FA over nanocrystals without FA modification. PTX NC@FA inhibited tumor growth more efficiently than both nanocrystals without FA modification and commercially available paclitaxel injection (Taxol) 12 days after peri-tumor injection. For model tumor with the volume of 100 mm3, tumors of all animals in the PTX NC@FA group disappeared completely. For model tumor with the volume of 300 mm3, tumors of 3 animals in the PTX NC@FA group completely disappeared and tumors of the rest 4 animals also became significantly smaller with a tumor volume inhibition rate of 90%. PTX NC@FA showed good potential for preoperative chemotherapy of increase the chances of function preserving gastrectomy and improve the quality of life of patients.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of a novel blockade technique for gastric cancer on blood-borne metastasis of gastric cancer cells to portal vein.</p><p><b>METHODS</b>Twenty-three cases of gastric cancer were divided into routine operation group (8 cases intraoperatively without blockade technique) and blockade group (15 cases with blockade technique). Blood samples from portal vein pre- and intraoperatively, as well as gastroepiploic vein limited within the blockade area were obtained to detect CK19 mRNA expression by using RT-PCR technique.</p><p><b>RESULTS</b>Before the dissection of gastric lesion, the overall positive rate of CK19 mRNA expression in portal vein blood is 34.7% (9/23), including 37.5% (3/8) in routine operation group and 33.3% (5/15) in blockade group. While the course of tumor resection, those positive rates were 87.5% (7/8) in routine operation group and 6.7% (1/15) in blockade group respectively (P < 0.05). CK19 mRNA expression in the right gastroepiploic venous blood limited within the blocking area was all positive in 15 cases of blockade group.</p><p><b>CONCLUSION</b>This blockade technique can be used effectively to block the intraoperative spread of gastric cancer cells, thus prevent blood-borne metastasis due to operative manipulation.</p>