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

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Lopes de Araujo, J (Author) Other; Salette Reis (Author) FFUP; Nunes, C (Author) Other

Journal

Title: European Journal of Pharmaceutical Sciences

Vol. 123

Pages: 515-523

ISSN: 0928-0987

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 2 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9