The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles

P. M. van Hasselt, G. E.P.J. Janssens, T. K. Slot, M. van der Ham, T. C. Minderhoud, M. Talelli, L. M. Akkermans, C. J.F. Rijcken, C. F. van Nostrum

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG5000-b-p(HPMAm-lac2), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, p < 0.01). Duodenal administration of polymeric micelles together with bile acids in bile duct ligated rats fully restored absorption. Dynamic light scattering time series showed a significant and dose dependent rise in micellar size in the presence of bile acids in vitro, indicating the gradual formation of mixed micelles during the first 3 h of incubation. The highest bile acid amounts (11 mM deoxycholic acid and 41 mM taurocholic acid) eventually caused aggregation of the loaded micelles after the formation of mixed micelles. These data suggest that the gastrointestinal absorption of encapsulated vitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.

Original languageEnglish
Pages (from-to)161-168
Number of pages8
JournalJournal of Controlled Release
Volume133
Issue number2
DOIs
Publication statusPublished - 19 Jan 2009

Cite this

van Hasselt, P. M., Janssens, G. E. P. J., Slot, T. K., van der Ham, M., Minderhoud, T. C., Talelli, M., ... van Nostrum, C. F. (2009). The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles. Journal of Controlled Release, 133(2), 161-168. https://doi.org/10.1016/j.jconrel.2008.09.089
van Hasselt, P. M. ; Janssens, G. E.P.J. ; Slot, T. K. ; van der Ham, M. ; Minderhoud, T. C. ; Talelli, M. ; Akkermans, L. M. ; Rijcken, C. J.F. ; van Nostrum, C. F. / The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles. In: Journal of Controlled Release. 2009 ; Vol. 133, No. 2. pp. 161-168.
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abstract = "The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG5000-b-p(HPMAm-lac2), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, p < 0.01). Duodenal administration of polymeric micelles together with bile acids in bile duct ligated rats fully restored absorption. Dynamic light scattering time series showed a significant and dose dependent rise in micellar size in the presence of bile acids in vitro, indicating the gradual formation of mixed micelles during the first 3 h of incubation. The highest bile acid amounts (11 mM deoxycholic acid and 41 mM taurocholic acid) eventually caused aggregation of the loaded micelles after the formation of mixed micelles. These data suggest that the gastrointestinal absorption of encapsulated vitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.",
keywords = "Bile acids, Block copolymers, Jaundice, Micelles, Oral administration, Vitamin K",
author = "{van Hasselt}, {P. M.} and Janssens, {G. E.P.J.} and Slot, {T. K.} and {van der Ham}, M. and Minderhoud, {T. C.} and M. Talelli and Akkermans, {L. M.} and Rijcken, {C. J.F.} and {van Nostrum}, {C. F.}",
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van Hasselt, PM, Janssens, GEPJ, Slot, TK, van der Ham, M, Minderhoud, TC, Talelli, M, Akkermans, LM, Rijcken, CJF & van Nostrum, CF 2009, 'The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles' Journal of Controlled Release, vol. 133, no. 2, pp. 161-168. https://doi.org/10.1016/j.jconrel.2008.09.089

The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles. / van Hasselt, P. M.; Janssens, G. E.P.J.; Slot, T. K.; van der Ham, M.; Minderhoud, T. C.; Talelli, M.; Akkermans, L. M.; Rijcken, C. J.F.; van Nostrum, C. F.

In: Journal of Controlled Release, Vol. 133, No. 2, 19.01.2009, p. 161-168.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - van Hasselt, P. M.

AU - Janssens, G. E.P.J.

AU - Slot, T. K.

AU - van der Ham, M.

AU - Minderhoud, T. C.

AU - Talelli, M.

AU - Akkermans, L. M.

AU - Rijcken, C. J.F.

AU - van Nostrum, C. F.

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N2 - The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG5000-b-p(HPMAm-lac2), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, p < 0.01). Duodenal administration of polymeric micelles together with bile acids in bile duct ligated rats fully restored absorption. Dynamic light scattering time series showed a significant and dose dependent rise in micellar size in the presence of bile acids in vitro, indicating the gradual formation of mixed micelles during the first 3 h of incubation. The highest bile acid amounts (11 mM deoxycholic acid and 41 mM taurocholic acid) eventually caused aggregation of the loaded micelles after the formation of mixed micelles. These data suggest that the gastrointestinal absorption of encapsulated vitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.

AB - The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG5000-b-p(HPMAm-lac2), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, p < 0.01). Duodenal administration of polymeric micelles together with bile acids in bile duct ligated rats fully restored absorption. Dynamic light scattering time series showed a significant and dose dependent rise in micellar size in the presence of bile acids in vitro, indicating the gradual formation of mixed micelles during the first 3 h of incubation. The highest bile acid amounts (11 mM deoxycholic acid and 41 mM taurocholic acid) eventually caused aggregation of the loaded micelles after the formation of mixed micelles. These data suggest that the gastrointestinal absorption of encapsulated vitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.

KW - Bile acids

KW - Block copolymers

KW - Jaundice

KW - Micelles

KW - Oral administration

KW - Vitamin K

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U2 - 10.1016/j.jconrel.2008.09.089

DO - 10.1016/j.jconrel.2008.09.089

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VL - 133

SP - 161

EP - 168

JO - Journal of Controlled Release

JF - Journal of Controlled Release

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