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Enhancing effect of N-octyl-O-sulfate chitosan on etoposide absorption.
Int J Pharm. 2011 May 16; 409(1-2):38-45.IJ

Abstract

P-glycoprotein (P-gp), expressed in the apical membranes of the epithelial cells of the intestine, can reduce the oral bioavailability of a wide range of drugs. Many surfactants/excipients have been demonstrated to potentially increase drug absorption by inhibiting P-gp. The purpose of the present study was to evaluate the effect of N-octyl-O-sulfate chitosan (NOSC) on the absorption of etoposide (VP16), a substrate of P-gp with low water solubility. The rat intestinal circulating perfusion in situ and Caco-2 cell uptake and monolayer membrane penetration in vitro were performed to investigate the enhancing ability of NOSC in comparison with some other P-gp inhibitors. The results indicated that various concentrations of NOSC all increased the intestinal absorption of VP16 in rat jejunum and ileum obviously and there was no significant difference in ileum between the enhancing effects of NOSC and other P-gp inhibitors. The VP16 uptake of Caco-2 cell was increased by NOSC solution with different concentrations. As the NOSC concentration was close to its critical micelle concentration (CMC), the cell uptake of VP16 reached to a maximum value. Both NOSC and verapamil (Ver) enhanced dramatically the transport of VP16 from apical side to basolateral side in Caco-2 cell monolayers. Moreover, they both decreased notably the transport of VP16 from basolateral side to apical side, but this effect of NOSC was weaker than that of Ver. However, transepithelial electrical resistance (TEER) of Caco-2 cell monolayers had no significant change during the study. These studies demonstrated that NOSC had the potential by inhibiting P-gp to improve the absorption of oral drugs which were P-gp substrates.

Authors+Show Affiliations

College of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21356302

Citation

Mo, Ran, et al. "Enhancing Effect of N-octyl-O-sulfate Chitosan On Etoposide Absorption." International Journal of Pharmaceutics, vol. 409, no. 1-2, 2011, pp. 38-45.
Mo R, Xiao Y, Sun M, et al. Enhancing effect of N-octyl-O-sulfate chitosan on etoposide absorption. Int J Pharm. 2011;409(1-2):38-45.
Mo, R., Xiao, Y., Sun, M., Zhang, C., & Ping, Q. (2011). Enhancing effect of N-octyl-O-sulfate chitosan on etoposide absorption. International Journal of Pharmaceutics, 409(1-2), 38-45. https://doi.org/10.1016/j.ijpharm.2011.02.021
Mo R, et al. Enhancing Effect of N-octyl-O-sulfate Chitosan On Etoposide Absorption. Int J Pharm. 2011 May 16;409(1-2):38-45. PubMed PMID: 21356302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancing effect of N-octyl-O-sulfate chitosan on etoposide absorption. AU - Mo,Ran, AU - Xiao,Yanyu, AU - Sun,Minjie, AU - Zhang,Can, AU - Ping,Qineng, Y1 - 2011/02/25/ PY - 2010/08/25/received PY - 2011/02/14/revised PY - 2011/02/17/accepted PY - 2011/3/2/entrez PY - 2011/3/2/pubmed PY - 2011/8/13/medline SP - 38 EP - 45 JF - International journal of pharmaceutics JO - Int J Pharm VL - 409 IS - 1-2 N2 - P-glycoprotein (P-gp), expressed in the apical membranes of the epithelial cells of the intestine, can reduce the oral bioavailability of a wide range of drugs. Many surfactants/excipients have been demonstrated to potentially increase drug absorption by inhibiting P-gp. The purpose of the present study was to evaluate the effect of N-octyl-O-sulfate chitosan (NOSC) on the absorption of etoposide (VP16), a substrate of P-gp with low water solubility. The rat intestinal circulating perfusion in situ and Caco-2 cell uptake and monolayer membrane penetration in vitro were performed to investigate the enhancing ability of NOSC in comparison with some other P-gp inhibitors. The results indicated that various concentrations of NOSC all increased the intestinal absorption of VP16 in rat jejunum and ileum obviously and there was no significant difference in ileum between the enhancing effects of NOSC and other P-gp inhibitors. The VP16 uptake of Caco-2 cell was increased by NOSC solution with different concentrations. As the NOSC concentration was close to its critical micelle concentration (CMC), the cell uptake of VP16 reached to a maximum value. Both NOSC and verapamil (Ver) enhanced dramatically the transport of VP16 from apical side to basolateral side in Caco-2 cell monolayers. Moreover, they both decreased notably the transport of VP16 from basolateral side to apical side, but this effect of NOSC was weaker than that of Ver. However, transepithelial electrical resistance (TEER) of Caco-2 cell monolayers had no significant change during the study. These studies demonstrated that NOSC had the potential by inhibiting P-gp to improve the absorption of oral drugs which were P-gp substrates. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/21356302/Enhancing_effect_of_N_octyl_O_sulfate_chitosan_on_etoposide_absorption_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(11)00156-6 DB - PRIME DP - Unbound Medicine ER -