Temozolomide encapsulated in zeolite structures as effective delivery systems of this drug in glioblastoma

Authors and Affiliations:

Olga Martinho,^a,b,c Natália Vilaça,^d Paulo J. G. Castro,^d Ricardo Amorim,^a,b António M. Fonseca,^d Fátima Baltazar,^a,b Rui M. Reis^a,b,c# and Isabel C. Neves^d#

^aLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, Braga, Portugal; ^bICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal; ^cMolecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; ^dCentre of Chemistry, Chemistry Department, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. 

Abstract:

Zeolites Y (faujasite) and MOR (mordonite) were used as a host for the temozolomide (TMZ), a current good-standard chemotherapeutic agent used in the treatment of glioblastoma brain tumors. TMZ was loaded into zeolites by liquid-phase adsorption at controlled pH. FTIR, 1H NMR, MS, SEM, UV/vis and chemical analysis demonstrated the successful loading of TMZ into zeolite hosts. The hydrolysis of TMZ in MTIC (TMZ metabolite) after the preparation of drug delivery systems (DDS) was observed in simulated body fluid. The effect of zeolites and DDS were evaluated on the viability of glioblastoma cell lines. Unloaded Y zeolite presented toxicity to cancer cells in contrast to MOR. In accordance, the best results in potentiation the TMZ effect was obtained with MOR. We found that mordonite loaded with 0.026 mmol of TMZ was able to decrease the half maximal inhibitory concentrations (IC₅₀) at least 3-fold in comparison to free temozolomide both in vitro and in vivo.

Journal: RSC Advances

Link: http://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra03871e#!divAbstract