The In Situ and In Vivo Study on Enhancing Effect of Borneol in Nasal Absorption of Geniposide in Rats

다국어 초록 (Multilingual Abstract)

The objective of this research was to study the in situ and in vivo nasal absorption of Geniposide (Ge) co-administered with borneol. A rat in situ nasal perfusion technique with a novel volumeadjusted calculation was used to examine the absorption rate and extent of Ge. The influence of different experimental conditions such as purity of extract, drug concentration, co-administration with synthetic borneol or natural borneol were also investigated. Results indicated nasal absorption of Ge was primarily by passive diffusion that resembled first order kinetics. Following co-administration with borenol, the drug absorption was increased by 1.4 and 1.7 folds for natural borneol and synthetic borneol , respectively. However, the effect of other factors on drug absorption was not significant. In addition, it was also observed that there is a positive correlation between the absorption of water and Ge by the nasal route. In vivo studies carried out in rats where Ge was co-administered with NB and the pharmacokinetic profile obtained following intranasal administration were compared with those after intravenous administration. The bioavailability of Ge by intranasal was 101.5% and Tmax was 2.04 ± 0.64 min. MRT was 218.7 ± 74.1 min and 44.4 ± 8.9 min for intranasal and intravenous, respectively. Combined with the borneol,Ge can be promptly and thoroughly absorbed intranasally in rats.

참고문헌 (Reference)

1 Illum, L, "Transport of drugs from the nasal cavity to the central nervous system" 11 : 1-18, 2000

2 Chavanpatil, M. D, "The influence of absorption enhancers on nasal absorption of acyclovir" 57 : 483-487, 2004

3 Merkus, F. W. H. M, "The influence of absorption enhancers on intranasal insulin absorption in normal and diabetic subjects" 41 : 69-75, 1996

4 Xiao, Y. Y, "The enhancing effect of synthetical borneol on the absorption of tetramethylpyrazine phosphate in mouse" 337 : 74-79, 2007

5 Hayashi, M, "Tetradine and isotetradine; two bisbenzyl tetra hydroisoquinoline alkaloids from merispemaceae with rat uterine smooth muscle relaxant activity" 33 : 2149-2152, 1983

6 Zhang, Q, "Studies on O/W partition coefficient and absorption kinetics of geniposide in fructus gardeniae extract in rat intestine" 34 : 1840-1844, 2009

7 Ueno, K, "Simultaneous estimation of geniposide and genipin in mouse plasma using high-performance liquid chromatography" 17 : 1237-1239, 2001

8 Duchìne, D, "Nasal administration: A tool of tomorrow’s systemic administration of drug" 19 : 101-122, 1993

9 Huang, C. H, "Mechanism of nasal absorption of drug I. Physicochemical parameters influencing the rate of in situ nasal absorption of drugs in rats" 74 : 608-611, 1985

10 Dai, J. P, "Influence of borneol on primary mice oral fibroblasts: A penetration enhancer may be used in oral submucous fibrosis" 38 : 276-281, 2009

11 Olivier, J. C, "In situ nasal absorption of midazolam in rats" 213 : 187-192, 2001

12 Ye, G, "HPLC method for the determination and pharmacokinetic studies on geniposide in rat serum after oral administration of traditional Chinese medicinal preparation Yin-Zhi-Ku decoction" 20 : 743-747, 2006

13 Chen, Y. M, "Effect of borneol on the intercellular tight junction and pinocytosis vesicles in vitro blood-brain barrier model" 24 : 632-634, 2004

14 Cai, Z, "Effect of borneol on the distribution of gastrodin to the brain in mice via oral administration" 16 : 178-184, 2008

15 Chen, X, "Effect of Absorption enhancer of borneol on ginsenoside Rg1 and the nasal ciliotoxicity" 41 : 261-264, 2006

16 Li, F, "Delivery of 125I-cobrotoxin after intranasal administration to the brain: A microdialysis study in freely moving rats" 328 : 161-167, 2007

17 Yang, C, "Chemical stability,enzymatic hydrolysis and nasal uptake of amino acid ester prodrugs of acyclovir" 90 : 617-624, 2001

18 Suzuki, Y, "Antithrombotic effect of geniposide and genipin in the mouse thrombosis model" 67 : 807-810, 2001

19 Koo, H.-J, "Antiinflammatory evaluation of gardenia extract geniposide and genipin" 103 : 496-500, 2006

20 Hirai, S, "Absorption of drugs from the nasal mucosa" 7 : 317-325, 1981