Temozolomide: An Overview of Biological Properties, Drug Delivery Nanosystems, and Analytical Methods

Author:

Chorilli Marlus1ORCID,Dutra Jessyca Aparecida Paes1ORCID,Luiz Marcela Tavares2ORCID,Tavares Junior Alberto Gomes1ORCID,Di Filippo Leonardo Delello1ORCID,Carvalho Suzana Gonçalves1ORCID

Affiliation:

1. School of Pharmaceutical Science, Sao Paulo State University (UNESP), Araraquara, Sao Paulo, Brazil

2. School of Pharmaceutical Science of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, São Paulo, Brazil

Abstract

Abstract: Temozolomide (TMZ) is an imidazotetrazine prodrug used to treat glioblastoma multiforme. Its physicochemical prop-erties and small size confer the ability to cross the blood-brain barrier. The antitumor activity depends on pH-dependent hydrolysis of the methyldiazonium cation, which is capable of methylating purine bases (O6-guanine; N7-guanine, and N3-adenine) and causing DNA damage and cell death. TMZ is more stable in acidic media (pH ≤ 5.0) than in basic media (pH ≥ 7.0) due to the protonated form that minimizes the catalytic process. Because of this, TMZ has high oral bioavailability, but it has a half-life of 1.8 h and low brain distribution (17.8%), requiring a repeated dos-ing regimen that limits its efficacy and increases adverse events. Drug delivery Nanosystems (DDNs) improve the phys-icochemical properties of TMZ and may provide controlled and targeted delivery. Therefore, DDNs can increase the efficacy and safety of TMZ. In this context, to ensure the efficiency of DDNs, analytical methods are used to evaluate TMZ pharmacokinetic parameters, encapsulation efficiency, and the release profile of DDNs. Among the methods, high-performance liquid chromatography is the most used due to its detection sensitivity in complex matrices such as tissues and plasma. Micellar electrokinetic chromatography features fast analysis and no sample pretreatment. Spec-trophotometric methods are still used to determine encapsulation efficiency due to their low cost, despite their low sen-sitivity. This review summarizes the physicochemical and pharmacological properties of free TMZ and TMZ-loaded DDNs. In addition, this review addresses the main analytical methods employed to characterize TMZ in different ma-trices.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery,Pharmacology

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