Derivative spectrophotometry as a tool for the determination of drug partition coefficients in water/dimyristoyl-L-alpha-phosphatidylglycerol (DMPG) liposomes

• Tipo: Artigo em Revista Científica Internacional
• Data: 2001

Autores

Rodrigues, C (Autor) Outra; Gameiro, P (Autor) FCUP; Reis, S (Autor) FFUP; Lima, JLFC (Autor) FFUP; de Castro, B (Autor) FCUP

Revista

Título: Biophysical Chemistry

Vol. 94

Páginas: 97-106

ISSN: 0301-4622

Editora: Elsevier

Indexação

ISI Web of Knowledge - 48 Citações

Scopus - 51 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-000-SES

DOI: 10.1016/s0301-4622(01)00227-7

Abstract (EN): The partition coefficients (K-p) between lipid bilayers of dimyristoyl-L-alpha -phosphatidylglycerol (DMPG) unilamellar liposomes and water were determined using derivative spectrophotometry for chlordiazepoxide (benzodiazepine), isoniazid and rifampicin (tuberculostatic drugs) and dibucaine (local anaesthetic). A comparison of the K-p values in water/DMPG with those in water/DMPC (dimyristoyl-L-alpha -phosphatidylcholine) revealed that for chlordiazepoxide and isoniazid, neutral drugs at physiological pH, the partition coefficients are similar in anionic (DMPG) and zwitterionic (DMPC) liposomes. However, for ionised drugs at physiological pH, the electrostatic interactions are different with DMPG and DMPC, with the cationic dibucaine having a stronger interaction with DMPG, and the anionic rifampicin having a much larger K-p in zwitterionic DMPC. These results show that liposomes are a better model membrane than an isotropic two-phase solvent system, such as water-octanol, to predict drub membrane partition coefficients, as they mimic better the hydrophobic part and the outer polar charged surface of the phospholipids of natural membranes.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10