Novel application of capillary electrophoresis with a liposome coated capillary for prediction of blood-brain barrier permeability.
Talanta
; 217: 121023, 2020 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-32498842
ABSTRACT
Profiling blood-brain barrier permeability of bioactive molecule is an important issue in early drug development, being a part of the optimization process of a compound's physicochemical properties, and hence pharmacokinetic profile. The study aimed to develop and optimize a new in vitro method for assessment of the compound's brain penetration. The tool is proposed as an alternative to the PAMPA-BBB (Parallel Artificial Membrane Permeability Assay for Blood-Brain Barrier) and based on a capillary electrochromatography (CEC) technique. It utilizes liposomes as structural substitutes of biological membranes, which are used as a capillary inner wall coating material. Following optimization of analysis conditions, migration times for a set of 25 reference drugs (mainly non-ionized in pH 7.4) were examined in a liposome coated capillary. On that basis, the retention factor (log k) was determined for each reference drug. Obtained log k values and experimentally received reference permeability parameters log BB (in vivo data) and log Pe (PAMPA-BBB data) were compared with one another. Correlation coefficients were calculated, giving comparable results for CEC log k/log BB and analogical PAMPA-BBB log Pe/log BB analyses. Approximate ranges of log k for the central nervous system (CNS) permeable (CNS(+)) and non-permeable (CNS(-)) drugs were established.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Barreira Hematoencefálica
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Talanta
Ano de publicação:
2020
Tipo de documento:
Article