Biophysical interaction of temozolomide and its active metabolite with biomembrane models: The relevance of drug-membrane interaction for Glioblastoma Multiforme therapy

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Maria João Ramalho (Author) FEUP; Stéphanie Andrade (Author) Other; Manuel Álvaro Neto Coelho (Author) FEUP; Joana Angélica Loureiro (Author) FEUP; Maria do Carmo Pereira (Author) FEUP

Journal

Title: European Journal of Pharmaceutics and Biopharmaceutics

Vol. 136

Pages: 156-163

ISSN: 0939-6411

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 16 Citations

Associated Projects

LEPABE - Projeto Estratégico do LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

LEPABE-2-ECO-INNOVATION - LEPABE-2-ECO-INNOVATION

Other information

Authenticus ID: P-00Q-9HV

DOI: 10.1016/j.ejpb.2019.01.015

Abstract (EN): Temozolomide (TMZ) is the first-line treatment for Glioblastoma Multiforme (GBM). After administration, TMZ is rapidly converted into its active metabolite (MTIC). However, its pharmacological activity is reduced due MTIC low bioavailability in the brain. Since drugs' permeability through biological barriers and tumor cell membranes affects its bioavailability, the ability of MTIC to interact with the biological membranes presents a major contribution on its pharmacological properties and activity. Biomembrane models mimic the physiological conditions, allowing to predict the drug's behavior at biological membranes and its effects on drug biodistribution profiles. In this work, lipid bilayer models using liposomes were applied for the drug-membrane interaction studies. The zwitterionlc phospholipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and cholesterol were chosen for the composition of the model, since they represent the major components of the membranes of GBM cells and brain capillary endothelial cell. Thus, the molecular interactions between MTIC and these models were studied by the evaluation of the partition of the drug into the phospholipid's membrane, its location within the bilayer and its effect on the fluidity of the membrane. The attained results suggest that the composition of membranes affects drugs partition, showing that drug biodistribution depends not only on its physicochemical features, but also depends on the characteristics of the membrane such as the packing of the lipid molecules. Also, MTIC exhibited low affinity to biological membranes, explaining its low bioavailability on the target cells.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8