Topotecan effect on the structure of normal and cancer plasma membrane lipid models: A multi-model approach

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Lopes de Araujo, J (Autor) Outra; Salette Reis (Autor) FFUP; Nunes, C (Autor) Outra

Revista

Título: European Journal of Pharmaceutical Sciences

Vol. 123

Páginas: 515-523

ISSN: 0928-0987

Editora: Elsevier

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 2 Citações

Outras Informações

ID Authenticus: P-00P-KEW

DOI: 10.1016/j.ejps.2018.08.006

Abstract (EN): Topotecan is a relatively large, planar, asymmetric and polar molecule with a lactone moiety. In neutral or basic aqueous solutions, this ring opens forming the carboxylate form of Topotecan that is biologically inactive and uncapable of passively cross membranes. Nevertheless, despite this inability to cross membranes at this form, Topotecan may still be able to interact with phospholipid bilayers, disturbing them. In this context, phospholipid models, mimicking normal (DMPC at pH 7.4) and cancer cell lipid membranes (DMPC:DMPS (5:1) at pH 6.5), were used to assess structural modifications upon interaction with Topotecan. Langmuir isotherms of monolayers coupled with Brewster angle microscopy, differential scanning calorimetry of liposomes and X-ray scattering of small and wide angle of stacked multilayers were used as complementary techniques. The overall results show that the interaction of Topotecan with lipid membranes is deeply conditioned by their composition and that Topotecan seems to have a preferential interaction with the glycerol backbone of phosphatidylcholine phospholipids.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9