Preparation and characterization of linolenic acid-chitosan micelle for doxorubicin oral delivery and its in situ intestinal absorption in rats
10.16438/j.0513-4870.2022-0343
- VernacularTitle:亚麻酸-壳聚糖载多柔比星口服胶束的制备和表征及大鼠在体肠吸收
- Author:
Yu-han YANG
1
;
Shi-yuan LIN
1
;
Hui CHEN
1
;
Dian-peng LI
2
;
Jian-fang FENG
3
;
Wei WU
1
;
Wei ZHANG
1
,
4
Author Information
1. School of Pharmacy, Guilin Medical University, Guilin 541004, China
2. Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China
3. School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China
4. Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China
- Publication Type:Research Article
- Keywords:
linolenic acid;
chitosan micelle;
oxorubicin;
italic>in situ single pass intestine perfusion model;
absorption
- From:
Acta Pharmaceutica Sinica
2022;57(9):2857-2863
- CountryChina
- Language:Chinese
-
Abstract:
In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of 1H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.
