MÄJLIGHETER MED LIPIDBASERADE BEREDNINGSFORMER UR ETT FYSIOLOGISKT OCH MOLEKYLÄRT PERSPEKTIV

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https://uu.diva-portal.org/smash/project.jsf?pid=project:4411

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Projekt

Projekttyp/Bidragsform

Projektbidrag

Titel [sv]

MÄJLIGHETER MED LIPIDBASERADE BEREDNINGSFORMER UR ETT FYSIOLOGISKT OCH MOLEKYLÄRT PERSPEKTIV - FOKUS P Å SV ÅRLÄSLIGA LÄKEMEDEL

Titel [en]

A MOLECULAR UNDERSTANDING OF LIPID BASED DRUG DELIVERY - A BRIDGE FOR POORLY SOLUBLE COMPOUNDS TO REACH PHYSIOLOGICAL TARGETS

Abstract [sv]

With 70-90% of the new drug-like molecules synthesised at date showing poor water solubility computational tools that allow predictions of the solubility and give suggestions on how to improve this property are warranted. We have previously developed computational models which identify for which reason aqueous solubility may be poor, and for compounds being lipophilic lipid based formulations (LBF) may improve the solubility in vivo. In this program we therefore: i) investigate if the solubility of drugs in lipid based formulations (LBF) can be predicted from chemical structure alone; ii) assess the capacity of the LBF to maintain a high concentration in the intestinal fluid, also after being subjected to lipolysis naturally occurring of these systems in vivo; and iii) assess the likelihood, amount and form of drug precipitate formed in vivo and its effects on the final intestinal concentration and absorption. The project is performed in silico, in vitro and in vivo. In all steps (i-iii), the obtained experimental results will be analyzed from a molecular perspective. Through this approach we believe it will be possible to computationally identify compounds which can be steered away from displaying poor solubility in vivo by use of LBF. Further, we can give guidelines on which excipients to include in formulations to enhance the solubility of compounds with solubility issues. Such guidelines would significantly improve the current drug discovery and development processes.

ProjektledareBergström, Christel Uppsala universitet

Koordinerande organisation

Uppsala universitet

Forskningsfinansiär

Vetenskapsrådet

Tidsperiod

2011-01-01 － 2013-12-31

Nationell ämneskategori

Farmaceutisk vetenskapMedicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)