Natural Lipid Extracts as an Artificial Membrane for Drug Permeability Assay: In Vitro and In Silico Characterization

Vincze, Anna and Dékány, Gergely and Bicsak, Richárd and Formanek, András and Moreau, Yves and Koplányi, Gábor and Takács, Gergely and Katona, Gábor and Balogh Weiser, Diána and Arany, Ádám and Balogh, György Tibor (2023) Natural Lipid Extracts as an Artificial Membrane for Drug Permeability Assay: In Vitro and In Silico Characterization. PHARMACEUTICS, 15 (3). No. 899. ISSN 1999-4923

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In vitro non-cellular permeability models such as the parallel artificial membrane permeability assay (PAMPA) are widely applied tools for early-phase drug candidate screening. In addition to the commonly used porcine brain polar lipid extract for modeling the blood–brain barrier’s permeability, the total and polar fractions of bovine heart and liver lipid extracts were investigated in the PAMPA model by measuring the permeability of 32 diverse drugs. The zeta potential of the lipid extracts and the net charge of their glycerophospholipid components were also determined. Physicochemical parameters of the 32 compounds were calculated using three independent forms of software (Marvin Sketch, RDKit, and ACD/Percepta). The relationship between the lipid-specific permeabilities and the physicochemical descriptors of the compounds was investigated using linear correlation, Spearman correlation, and PCA analysis. While the results showed only subtle differences between total and polar lipids, permeability through liver lipids highly differed from that of the heart or brain lipid-based models. Correlations between the in silico descriptors (e.g., number of amide bonds, heteroatoms, and aromatic heterocycles, accessible surface area, and H-bond acceptor–donor balance) of drug molecules and permeability values were also found, which provides support for understanding tissue-specific permeability.

Item Type: Article
Uncontrolled Keywords: natural lipid extract; total and polar lipids; brain–heart–liver lipids; tissue-specific permeability; PAMPA; physicochemical and in silico characterization
Subjects: Q Science / természettudomány > QC Physics / fizika > QC173.4 Material science / anyagtudomány
Q Science / természettudomány > QD Chemistry / kémia > QD02 Physical chemistry / fizikai kémia
R Medicine / orvostudomány > RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Depositing User: MTMT SWORD
Date Deposited: 25 Sep 2023 08:07
Last Modified: 25 Sep 2023 08:07

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