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.
ABSTRACT
Objective: To explore the protective effect of formula of Gougancai decoction (FGD) on acute liver injury induced by carbon tetrachloride (CCl4) in rats, in order to provide basis for the development of pharmaceutical preparations or healthcare products. Method: Sixty rats were randomly divided into normal group, Silymarin group (120 mg·kg-1) and FGD groups (475, 950, 1 900 mg·kg-1). The normal group and the model group were given equal volume of saline by gavage, while the other groups were administered with the corresponding dose of drugs according to the body weight. After 10 days, the acute liver injury model was established with 12% carbon tetrachloride peanut oil solution (5 mL·kg-1), except the normal group. All of the rats were put to death to collect serum and liver tissues. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected by biochemical methods, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in liver tissues were determined by enzyme-linked immunosorbnent assay(ELISA). Nuclear factor-κB (NF-κB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expression in liver tissues were detected by Western blot, and htoxylin eosin (HE) staining was used to observe the variation of liver histopathological. Result: Compared with the normal group, the serum activities of AST, ALT, ALP and the content of TBIL, MDA in the model group were significantly increased (Pα, IL-1β, IL-6 in liver tissue were remarkably increased (PPκB was enhanced in liver tissue (Pγ was down-regulated (PPPα, IL-1β, IL-6 (PPκB (PPγ (PPConclusion: FGD has a protective effect on CCl4-induced acute liver injury in rats, and its mechanism may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling pathway, with anti-inflammatory and anti-oxidative effects.