Preparation, Characterization and Anti-Ulcer Efficacy of Sanguinarine Loaded Solid Lipid Nanoparticles.
OBJECTIVE
This study was designed to develop sanguinarine-loaded solid lipid nanoparticles (SG-SLNs) and investigate its gastroprotective effect on ethanol-induced gastric mucosal lesions in mice.


METHODS
SG-SLNs were prepared by high temperature melt-cool solidification method using glycerol monostearate as the lipid and a combination of lecithin with poloxamer 188 as the surfactants. Solid lipid nanoparticles (SLNs) were designed at varying lipid concentrations (5, 10, 15, and 20 mg/mL), surfactant mixture concentrations (6, 12, and 18 mg/mL), and drug contents (5, 10, 15, and 20 mg/mL) in "one factor at a time" fashion. Ethanol-induced gastric ulcer model was performed on Kunming mice to examine the anti-inflammatory activity of SG-SLNs and compare it with sanguinarine (SG).


RESULTS
The high temperature melt-cool solidification method provided consistent production of SLNs with smaller size and high entrapment efficiency (EE%). The composition of optimal formulation was 10 mg/mL lipid concentration, 18 mg/mL surfactant mixture concentration, and 15 mg/mL drug amount. The mean particle size and EE% of optimized formulation were 238 ± 10.9 nm and 79 ± 2.8%, respectively. Additionally, SG-SLNs significantly decreased tumor necrosis factor-alpha and interleukin-6 levels in the serum and gastric tissue, and reduced the content of NO in serum, and strengthened the protection of mucosal membrane. Moreover, SG-SLNs treatment markedly inhibited ethanol-induced nuclear factor-kappa B (NF-κB) activation when compared with SG.


CONCLUSIONS
SLNs could be potentially applied as a delivery system of SG. The protective effect of SG-SLNs is due to the suppression of NF-κB expression and subsequent pro-inflammatory cytokines release.
Department of Pharmacy, the First Affiliated Hospital of Medicine College, Xi'an, China.
Qing
Q
Sun
Weifeng
W
Li
Huani
H
Li
Xiumei
X
Wang
Yu
Y
Wang
Xiaofeng
X
Niu
D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology; D053119:Benzophenanthridines / Q000008:administration & dosage / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D000431:Ethanol / Q000633:toxicity; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D054709:Lecithins / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D013276:Stomach Ulcer / Q000517:prevention & control*; D013501:Surface-Active Agents / Q000737:chemistry
D000897:Anti-Ulcer Agents; D053119:Benzophenanthridines; D004337:Drug Carriers; D007546:Isoquinolines; D054709:Lecithins; D008055:Lipids; D016328:NF-kappa B; D013501:Surface-Active Agents; D020442:Poloxamer; D000431:Ethanol; C005705:sanguinarine
Gastric ulcer; Nuclear factor-kappa B; Pro-inflammatory cytokines; Sanguinarine; Solid lipid nanoparticles