Folic acid-modified phospholipid-encapsulated paclitaxel nanocrystals for preoperative chemotherapy of gastric cancer
10.16438/j.0513-4870.2021-1247
- VernacularTitle:基于胃癌术前化疗的叶酸修饰磷脂包被紫杉醇纳米晶制剂研究
- Author:
Jun WANG
1
;
Guang-jian HUANG
2
;
Yu LIU
1
;
Wei-yue LU
1
Author Information
1. Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China
2. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
- Publication Type:Research Article
- Keywords:
paclitaxel;
nanocrystal;
folic acid-modified phospholipid;
gastric cancer;
peritumoral injection;
preoperative chemotherapy
- From:
Acta Pharmaceutica Sinica
2022;57(1):233-241
- CountryChina
- Language:Chinese
-
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.
