Title:Temozolomide: An Overview of Biological Properties, Drug Delivery Nanosystems,
and Analytical Methods
Volume: 28
Issue: 25
Author(s): Jessyca Aparecida Paes Dutra, Marcela Tavares Luiz, Alberto Gomes Tavares Junior, Leonardo Delello Di Filippo, Suzana Gonçalves Carvalho and Marlus Chorilli*
Affiliation:
- School of Pharmaceutical Science, Sao Paulo State University (UNESP), Araraquara, Sao Paulo, Brazil
Keywords:
Temozolomide metabolites, physicochemical properties, drug delivery, nanomedicines, chromatography, spectroscopy, electrophoresis.
Abstract: Temozolomide (TMZ) is an imidazotetrazine prodrug used to treat glioblastoma multiforme. Its
physicochemical properties 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. Due to 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 dosing regimen that limits its efficacy and increases adverse events.
Drug delivery Nanosystems (DDNs) improve the physicochemical 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. Spectrophotometric methods
are still used to determine encapsulation efficiency due to their low cost, despite their low sensitivity. 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
matrices.