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INTESTINANOS SIGNED

Intestinal Lipoidal Nanostructures - A Lipid Bridge to Increased Drug Delivery

Total Cost €

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EC-Contrib. €

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Partnership

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Project "INTESTINANOS" data sheet

The following table provides information about the project.

Coordinator
UPPSALA UNIVERSITET 

Organization address
address: VON KRAEMERS ALLE 4
city: UPPSALA
postcode: 751 05
website: www.uu.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Sweden [SE]
 Total cost 1˙706˙250 €
 EC max contribution 1˙706˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-09-01   to  2020-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UPPSALA UNIVERSITET SE (UPPSALA) coordinator 1˙706˙250.00

Map

 Project objective

My research program explores molecular interplay between drug, dosage form and the complex environment of the gastrointestinal tract (GIT). Drug molecules currently being discovered to cure e.g. CNS diseases, cancer and the metabolic syndrome show poor water solubility and 70-90% of recently discovered drugs have too poor solubility to allow absorption from the GIT. For such compounds the dosage form can significantly improve the absorption. My long-term goal is to establish a computational platform that predicts, from molecular structures and computational tools, the development potential of drug molecules to well-functioning orally administered medicines. A major gap to understand drug performance in the intestine is the poor knowledge of the dynamics of solubilizing lipoidal nanostructures (micelles, vesicles, oil droplets) present in the fluid. This project explores restructuring of these lipid colloids in response to intake of food or dosage forms, enzymatic digestion, absorption and transit along the GIT. Novel experimental tools are developed to reveal the impact of these nanostructures on drug solubilization, supersaturation and likelihood of precipitation in vivo, all being important for drug absorption. The experimental results are fed into in silico models taking use of Molecular Dynamics simulations to develop a computational platform predicting drug performance in the dynamic intestinal milieu. The novel tools designed herein will allow dosage forms that improve performance and increase drug absorption after oral administration to, for the first time, be designed by computational means. The results of this project, in particular the novel in silico tools exploring rearrangement of lipoidal nanostructures, are highly important to related areas such as GIT disease models and food processing but also have wider applications in e.g. studies of intracellular vesicle rearrangements and transport processes in plants.

 Publications

year authors and title journal last update
List of publications.
2017 Per Larsson, Linda C. Alskär, Christel A. S. Bergström
Molecular Structuring and Phase Transition of Lipid-Based Formulations upon Water Dispersion: A Coarse-Grained Molecular Dynamics Simulation Approach
published pages: 4145-4153, ISSN: 1543-8384, DOI: 10.1021/acs.molpharmaceut.7b00397
Molecular Pharmaceutics 14/12 2019-05-29
2018 Christel A.S. Bergström, Per Larsson
Computational prediction of drug solubility in water-based systems: Qualitative and quantitative approaches used in the current drug discovery and development setting
published pages: 185-193, ISSN: 0378-5173, DOI: 10.1016/j.ijpharm.2018.01.044
International Journal of Pharmaceutics 540/1-2 2019-05-29
2017 Andrew J. Clulow, Albin Parrow, Adrian Hawley, Jamal Khan, Anna C. Pham, Per Larsson, Christel A. S. Bergström, Ben J. Boyd
Characterization of Solubilizing Nanoaggregates Present in Different Versions of Simulated Intestinal Fluid
published pages: 10869-10881, ISSN: 1520-6106, DOI: 10.1021/acs.jpcb.7b08622
The Journal of Physical Chemistry B 121/48 2019-05-29
2018 Janneke Keemink, Christel A. S. Bergström
Caco-2 Cell Conditions Enabling Studies of Drug Absorption from Digestible Lipid-Based Formulations
published pages: , ISSN: 0724-8741, DOI: 10.1007/s11095-017-2327-8
Pharmaceutical Research 35/4 2019-05-29
2015 Amjad Alhalaweh, Ahmad Alzghoul, Denny Mahlin, Christel A.S. Bergström
Physical stability of drugs after storage above and below the glass transition temperature: Relationship to glass-forming ability
published pages: 312-317, ISSN: 0378-5173, DOI: 10.1016/j.ijpharm.2015.08.101
International Journal of Pharmaceutics 495/1 2019-04-18
2018 Linda C Alskär, Janneke Keemink, Jenny Johannesson, Christopher JH Porter, Christel AS Bergström
Impact of Drug Physicochemical Properties on Lipolysis-triggered Drug Supersaturation and Precipitation from Lipid-Based Formulations
published pages: , ISSN: 1543-8384, DOI:
Molecular Pharmaceutics 2019-04-18
2017 Khadijah Edueng, Denny Mahlin, Christel A. S. Bergström
The Need for Restructuring the Disordered Science of Amorphous Drug Formulations
published pages: 1754-1772, ISSN: 0724-8741, DOI: 10.1007/s11095-017-2174-7
Pharmaceutical Research 34/9 2019-04-18
2015 Linda C. Alskär, Christel A. S. Bergström
Models for Predicting Drug Absorption From Oral Lipid-Based Formulations
published pages: 141-147, ISSN: 2198-6428, DOI: 10.1007/s40610-015-0023-1
Current Molecular Biology Reports 1/4 2019-05-27
2016 Michael Holmboe, Per Larsson, Jamshed Anwar, Christel A. S. Bergström
Partitioning into Colloidal Structures of Fasted State Intestinal Fluid Studied by Molecular Dynamics Simulations
published pages: 12732-12740, ISSN: 0743-7463, DOI: 10.1021/acs.langmuir.6b03008
Langmuir 32/48 2019-05-27
2016 Linda C. Alskär, Christopher J. H. Porter, Christel A. S. Bergström
Tools for Early Prediction of Drug Loading in Lipid-Based Formulations
published pages: 251-261, ISSN: 1543-8384, DOI: 10.1021/acs.molpharmaceut.5b00704
Molecular Pharmaceutics 13/1 2019-05-27
2016 Christel A.S. Bergström, William N. Charman, Christopher J.H. Porter
Computational prediction of formulation strategies for beyond-rule-of-5 compounds
published pages: 6-21, ISSN: 0169-409X, DOI: 10.1016/j.addr.2016.02.005
Advanced Drug Delivery Reviews 101 2019-05-27
2017 Khadijah Edueng, Denny Mahlin, Per Larsson, Christel A.S. Bergström
Mechanism-based selection of stabilization strategy for amorphous formulations: Insights into crystallization pathways
published pages: , ISSN: 0168-3659, DOI: 10.1016/j.jconrel.2017.04.015
Journal of Controlled Release 256 2019-05-27
2015 Pär Matsson, Christel A S Bergström
Computational modeling to predict the functions and impact of drug transporters
published pages: , ISSN: 2193-9616, DOI: 10.1186/s40203-015-0012-3
In Silico Pharmacology 3/1 2019-05-27

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