Molecular Dynamics Simulations on Interindividual Variability of Intestinal Fluids: Impact on Drug Solubilization.
MD simulations
coarse-grained simulations
drug solubility
intestinal fluids
micelles
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
05 10 2020
05 10 2020
Historique:
pubmed:
14
8
2020
medline:
3
8
2021
entrez:
14
8
2020
Statut:
ppublish
Résumé
Efficient delivery of oral drugs is dependent on their solubility in human intestinal fluid, a complex and dynamic fluid that contains colloidal structures composed of small molecules. These structures solubilize poorly water-soluble compounds, increasing their apparent solubility, and possibly their bioavailability. In this study, we conducted coarse-grained molecular dynamics simulations with data from duodenal fluid samples previously acquired from five healthy volunteers. In these simulations, we observed the self-assembly of mixed micelles of bile salts, phospholipids, and free fatty acids. The micelles were ellipsoids with a size range of 4-7 nm. Next, we investigated micelle affinities of three model drugs. The affinities in our simulation showed the same trend as literature values for the solubility enhancement of drugs in human intestinal fluids. This type of simulations is useful for studies of events and interactions taking place in the small intestinal fluid.
Identifiants
pubmed: 32787279
doi: 10.1021/acs.molpharmaceut.0c00588
pmc: PMC7704030
doi:
Substances chimiques
Micelles
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3837-3844Références
J Am Chem Soc. 2001 Sep 5;123(35):8638-9
pubmed: 11525689
Mol Pharm. 2017 Mar 6;14(3):566-579
pubmed: 28099023
J Phys Chem B. 2017 Aug 24;121(33):7878-7888
pubmed: 28737387
J Phys Chem B. 2017 Dec 7;121(48):10869-10881
pubmed: 29090933
J Lipid Res. 2007 Jan;48(1):242-51
pubmed: 17062898
Eur J Pharm Biopharm. 2018 Aug;129:104-110
pubmed: 29802985
J Am Chem Soc. 2011 Oct 19;133(41):16524-36
pubmed: 21823595
J Pharm Sci. 2016 Feb;105(2):673-681
pubmed: 26228456
J Chem Inf Model. 2017 Apr 24;57(4):650-656
pubmed: 28345910
Eur J Pharm Sci. 2011 Jul 17;43(4):260-9
pubmed: 21570465
J Chem Theory Comput. 2017 Oct 10;13(10):5039-5053
pubmed: 28787166
J Chem Theory Comput. 2015 Jun 9;11(6):2783-91
pubmed: 26575571
Eur J Pharm Sci. 2018 Jul 30;120:61-72
pubmed: 29704643
Ther Deliv. 2015;6(8):935-59
pubmed: 26316058
J Am Chem Soc. 2003 Dec 10;125(49):15233-42
pubmed: 14653758
Mol Pharm. 2016 Oct 3;13(10):3484-3493
pubmed: 27576295
Biochemistry. 2002 Apr 30;41(17):5375-82
pubmed: 11969397
AAPS J. 2010 Sep;12(3):397-406
pubmed: 20458565
J Colloid Interface Sci. 2017 Aug 1;499:189-201
pubmed: 28384537
Langmuir. 2016 Dec 6;32(48):12732-12740
pubmed: 27934534
Mol Pharm. 2012 Feb 6;9(2):237-47
pubmed: 22136289
Biophys Chem. 2019 May;248:16-27
pubmed: 30850307
J Pharm Pharmacol. 2015 Apr;67(4):486-92
pubmed: 25580567
Langmuir. 2007 Nov 20;23(24):12322-8
pubmed: 17944496
J Chem Inf Model. 2020 Feb 24;60(2):522-536
pubmed: 31714768
J Phys Chem B. 2014 Apr 3;118(13):3593-604
pubmed: 24533791
J Pharm Sci. 1996 Jan;85(1):9-15
pubmed: 8926591
J Pharm Sci. 2009 Mar;98(3):1177-92
pubmed: 18680176
Mol Pharm. 2010 Oct 4;7(5):1498-507
pubmed: 20698569
J Am Chem Soc. 2007 Dec 19;129(50):15414-5
pubmed: 18034478
Nature. 1990 Oct 18;347(6294):631-9
pubmed: 2215695
J Chem Theory Comput. 2013 Jan 8;9(1):687-97
pubmed: 26589065
J Phys Chem B. 2007 Jul 12;111(27):7812-24
pubmed: 17569554