Abstract
Borneol, a monoterpenoid alcohol, is used widely, particularly in combined formulas for preventing and curing cardiovascular and cerebrovascular diseases in traditional Chinese medicine. In order to understand the blood and brain pharmacokinetics after intravenous, intranasal, or oral administration and to investigate the superiority and feasibility of intranasal administration, a simple gas chromatographic (GC) method with flame ionization detection (FID) was developed for the quantification of borneol. Blood samples and brain were collected from mice at 1, 3, 5, 10, 20, 30, 60, 90, and 120 min after intravenous, intranasal, or oral administration of borneol at a dosage of 30.0 mg/kg. Sample preparations were carried out by liquid-liquid extraction with an internal standard solution of octadecane. The pharmacokinetic parameters were calculated by the software of Kinetica. The calibration curves were linear in the range of 0.11–84.24 μg/ml and 0.16–63.18 μg/g for borneol in plasma and brain, respectively. The methodological and extraction recoveries were both in the range of 85%–115%. The intra-day and inter-day variabilities for plasma and brain samples were ≤5.00% relative standard deviation (RSD). The absolute bioavailabilities F of intranasal and oral administrations were 90.68% and 42.99%. The relative brain targeted coefficients Re of intranasal and oral administrations were 68.37% and 38.40%. The GC-FID method developed could be applied to determination and pharmacokinetic study. The borneol from injection was distributed and metabolized fast without absorption process. The borneol from oral administration was distributed more slowly and had the lowest absolute bioavailability. Nasal administration of borneol was quickly absorbed into the blood and brain, was easy to use and had a greater safety than infection, which makes it worthy of further development as an administration route for encephalopathy treatment.
Similar content being viewed by others
References
Arora, P., Sharma, S., Garg, S., 2002. Permeability issues in nasal drug delivery. Drug discov. Today, 7(18):967–975. [doi:10.1016/S1359-6446(02)02452-2]
Born, J., Lange, T., Kern, W., McGregor, G.P., Bickel, U., Fehm, H.L., 2002. Sniffing neuropeptides: a transnasal approach to the human brain. Nat. Neurosci., 5(6):514–516. [doi:10.1038/nn0602-849]
Cai, Z., Hou, S., Li, Y., Zhao, B., Yang, Z., Xu, S., Pu, J., 2008. Effect of borneol on the distribution of gastrodin to the brain in mice via oral administration. J. Drug Target., 16(2):178–184. [doi:10.1080/10611860701794395]
Costantino, H.R., Illum, L., Brandt, G., 2007. Intranasal delivery: physicochemical and therapeutic aspects. Int. J. Pharm., 337(1–2):1–24. [doi:10.1016/j.ijpharm.2007.03.025]
Dai, J.P., Chen, J., Bei, Y.F., Han, B.X., Wang, S., 2009. Influence of borneol on primary mice oral fibroblasts: a penetration enhancer may be used in oral submucous fibrosis. J. Oral Pathol. Med., 38(3):276–281. [doi:10. 1111/j.1600-0714.2008.00738.x]
Dhuria, S.V., Hanson, L.R., Frey, W.H., 2009. Novel vasoconstrictor formulation to enhance intranasal targeting of neuropeptide therapeutics to the central nervous system. J. Pharmacol. Exp. Ther., 328(1):312–320. [doi:10.1124/jpet.108.145565]
Dhuria, S.V., Hanson, L.R., Frey, W.H., 2010. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J. Pharm. Sci., 99(4):1654–1673. [doi:10.1002/jps.21924]
Elshafeey, A.H., Bendas, E.R., Mohamed, O.H., 2009. Intranasal microemulsion of sildenafil citrate: in vitro evaluation and in vivo pharmacokinetic study in rabbits. AAPS PharmSciTech., 10(2):361–367. [doi:10.1208/s12249-009-9213-6]
Garcia-Rodriguez, J.C., Sosa-Teste, I., 2009. The nasal route as a potential pathway for delivery of erythropoietin in the treatment of acute ischemic stroke in humans. Sci. World J., 9:970–981. [doi:10.1100/tsw.2009.103]
Hanson, L.R., Frey, W.H., 2008. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci., 9(S3):S5. [doi:10.1186/1471-2202-9-S3-S5]
Hanson, L.R., Roeytenberg, A., Martinez, P.M., Coppes, V.G., Sweet, D.C., Rao, R.J., Marti, D.L., Hoekman, J.D., Matthews, R.B., Frey II, W.H., et al., 2009. Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. J. Pharmacol. Exp. Ther., 330(3):679–686. [doi:10.1124/jpet.108.149807]
Huang, P., Jiang, X.F., Zou, J.L., Yuan, Y.M., Yao, M.C., Lu, Y.S., 2009. A novel GC-MS bioanalytical method for natural borneol and its application in investigating natural borneol distribution in mice. Mode. Tradit. Chin. Med. Mater. Med., 11(6):821–827. [doi:10.1016/s1876-3553(10)60038-5]
Li, F., Feng, J., Cheng, Q., Zhu, W., Jin, Y., 2007. Delivery of 125I-cobrotoxin after intranasal administration to the brain: a microdialysis study in freely moving rats. Int. J. Pharm., 328(2):161–167. [doi:10.1016/j.ijpharm.2006. 08.011]
Li, W.R., Chen, R.Y., Yang, L., 2012. Pharmacokinetics of natural borneol after oral administration in mice brain and its effect on excitation ratio. Eur. J. Drug Metab. Pharmacokinet, 37:39–44. [doi:10.1007/s13318-011-0058-5]
Lochhead, J.J., Thorne, R.G., 2012. Intranasal delivery of biologics to the central nervous system. Adv. Drug Deli. Rev., 64(7):614–628. [doi:10.1016/j.addr.2011.11.002]
Lu, Y., Chen, X.L., Du, S.Y., Wu, Q., Yao, Z.L., Zhai, Y.S., 2010. The in situ and in vivo study on enhancing effect of borneol in nasal absorption of geniposide in rats. Arch. Pharm. Res., 33(5):691–696. [doi:10.1007/s12272-010-0507-8]
Lu, Y., Du, S.Y., Chen, X.L., Li, P.Y., Zhai, Y.S., Wu, Q., Li, D.X., 2011a. Study on pharmacokinetics of borneol in rats injected with novel-Xingnaojing by GC-FID. China J. Chin. Mat. Med., 36(16):2200–2202 (in Chinese). [doi:10.4268/cjcmm20111610]
Lu, Y., Du, S.Y., Chen, X.L., Wu, Q., Song, X., Xu, B., Zhai, Y.S., 2011b. Enhancing effect of natural borneol on the absorption of geniposide in rat via intranasal administration. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 12(2):143–148. [doi:10.1631/jzus.B1000121]
Ma, Y., Du, S.Y., Song, X., Lu, Y., Li, D.X., 2011. Study on the intestinal absorption kinetics of aipian in rats. China Pharm., 22(39):3651–3653 (in Chinese).
Pillion, D.J., Fyrberg, M.D., Meezan, E., 2010. Nasal absorption of mixtures of fast-acting and long-acting insulins. Int J. Pharm., 388(1–2):202–208. [doi:10.1016/j.ijpharm. 2010.01.013]
Song, X., Du, S.Y., Lu, Y., Ma, Y., Chen, X.L., Wang, Y., Zhang, H.X., 2011. Study on rat nasal absorption in situ of borneol based on single pass perfusion method. China J. Chin. Mat. Med., 36(18):2489–2492 (in Chinese). [doi:10.4268/cjcmm20111808]
State Pharmacopoeia Committee of People’s Republic of China, 2010. Chinese Pharmacopoeia. The Medicine Science and Technology Press of China, Beijing, China, p.82 (in Chinese).
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by the Key New Drug Creation and Development Programme of China (No. 2009ZX09502-008), the National Natural Science Foundation of China (No. 81073057), and the Innovation Team Development Program of Beijing University of Chinese Medicine (No. 2011-CXTD-13)
Rights and permissions
About this article
Cite this article
Zhao, Jy., Lu, Y., Du, Sy. et al. Comparative pharmacokinetic studies of borneol in mouse plasma and brain by different administrations. J. Zhejiang Univ. Sci. B 13, 990–996 (2012). https://doi.org/10.1631/jzus.B1200142
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B1200142