3-4-dihydroxyphenyllactic-acid and isoborneol

Tanshinol borneol ester (DBZ) is a hybrid of danshensu (DSS) and borneol and has anti-ischemic activity in animals. However, its low water solubility and short half-life limit its clinical application.. We prepared polyethylene glycol (PEG)-modified and DBZ-loaded nanostructured lipid carriers (DBZ-PEG-NLC) and DBZ-NLC, and examined their physical characteristics, such as particle size, zeta potential, entrapment efficiency and drug loading. The in vitro stability and pharmacokinetics in rats as well as antioxidant activity of DBZ-PEG-NLC and DBZ-NLC in a C57BL/6 mouse model of ischemia/reperfusion-related brain injury were investigated. The levels of DBZ and its hydrolyzed DSS in rat plasma and brain microdialysates were determined by liquid chromatography-mass spectroscopy/mass spectroscopy analysis.. We found that the mean particle size and entrapment efficacy of DBZ-PEG-NLC were similar to that of DBZ-NLC. The DBZ-PEG-NLC, like DBZ-NLC, released DBZ in a biphasic manner with initially burst release and then prolonged slow release in vitro. Intravenous injection of DBZ-PEG-NLC resulted in significantly higher levels and longer retention periods of DBZ and DSS in plasma and the brains than DBZ-NLC and DBZ in rats. Finally, treatment with DBZ-PEG-NLC achieved a better antioxidant activity than DBZ or DBZ-NLC in mouse model of ischemia/reperfusion by reducing the levels of brain malondialdehyde, but increasing the levels of brain superoxide dismutase and glutathione.. DBZ-PEG-NLC is a preferable option to deliver DBZ for sustainable release of DSS and borneol in vivo, and may serve as a promising drug for effective therapy of ischemic cardiovascular and cerebrovascular diseases.

Topics: Animals; Antioxidants; Brain; Camphanes; Drug Carriers; Drug Liberation; Drug Stability; Half-Life; Lactates; Lipids; Male; Mice, Inbred C57BL; Nanostructures; Particle Size; Polyethylene Glycols; Rats, Sprague-Dawley; Solubility

Both borneol and danshensu are bioactive substances derived from traditional Chinese medicine. In this paper, the effect of borneol on the distribution of danshensu to the eyes in rabbits via oral administration was investigated.. The rabbits were injected danshensu (1.0 g/kg) into the auris dextra vein 15 min after intragastric administration of borneol and the danshensu concentrations in plasma, aqueous humor, and vitreous humor were measured by high-performance liquid chromatography. Draize test was used to examine the eye irritation.. Compared with the administration of danshensu alone, danshensu concentrations co-administrated with borneol in plasma were between 60.99 and 722.90 microg/ml. Peak times (T(max)) in both groups appeared at 0 min; however, compared with the control group, the values were not statistically significant although they differ (P > 0.05). The concentrations of danshensu in aqueous humor and vitreous humor in test group are higher than that in control group. The difference was statistically significant (P < 0.05). T(max) in both groups appeared at 25 min. Neither irritation nor inflammatory reaction was found during the examinations.. The results suggest that the promoting effect of borneol on the permeability of drugs through the blood-ocular barrier in vivo is obvious, which indicates that borneol has the potential to be used as an ocular penetration enhancer.

Topics: Administration, Oral; Animals; Aqueous Humor; Biological Availability; Biological Transport; Blood-Aqueous Barrier; Blood-Retinal Barrier; Camphanes; Chromatography, High Pressure Liquid; Cornea; Drugs, Chinese Herbal; Female; Lactates; Male; Rabbits; Vitreous Body