175
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_14,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 14
Encapsulation of Small Drugs in a Supramolecule
Enhances Solubility, Stability, and Therapeutic Efficacy
Against Glioblastoma Multiforme
Antonis D. Tsiailanis, Alexander Renziehausen, Serdar Karakurt,
Tim Crook, Nelofer Syed, and Andreas G. Tzakos
Abstract
Cancer occupies a high rank in the global morbidity and mortality scale with glioblastoma multiforme
(GBM) accounting for almost 80% of all primary tumors of the brain. Despite the increasing availability of
targeted and immunotherapeutic agents, chemotherapy still plays an important role in the treatment of
neoplastic diseases. Limitations to the effective use of chemotherapy such as low aqueous solubility and
high toxicity have directed the scientific community’s interest to the development of new therapeutic
agents with enhanced efficacy and limited toxicity. Supramolecular chemistry has offered an alternative way
on the design and development of new therapeutic agents as a result of their unique properties.
Supramolecules can be used as drug carriers since their cavities can host a wide range of small drugs and
surpass in this way the drawbacks of current therapeutic agents. Herein, we present the principles that
should be followed for the encapsulation of small drugs in supramolecules with enhanced physicochemical
properties and increased efficacy against glioblastoma multiforme.
Key words Glioblastoma multiforme, Temozolomide, Supramolecule, p-sulfonatocalix[4]arene,
Encapsulation,
1
H-NMR spectroscopy, Mass spectrometry, Liquid chromatography, LC-MS/MS
1 Introduction
Cancer is one of the leading global causes of morbidity and mortality. Although targeted and immunotherapeutic agents are increasingly available, systemic chemotherapy continues to have an
important role in the management of the neoplastic disease.
Despite obvious benefits of chemotherapy, its utility is frequently
limited, particularly in metastatic disease, by innate and/or
acquired drug resistance (the latter an inevitable consequence of
tumor heterogeneity) and by toxicity of drugs [1]. Further limitations to the effective use of chemotherapy arise due to poor aqueous solubility, instability, and low drug-loading capacity. The ability
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_14,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 14
Encapsulation of Small Drugs in a Supramolecule
Enhances Solubility, Stability, and Therapeutic Efficacy
Against Glioblastoma Multiforme
Antonis D. Tsiailanis, Alexander Renziehausen, Serdar Karakurt,
Tim Crook, Nelofer Syed, and Andreas G. Tzakos
Abstract
Cancer occupies a high rank in the global morbidity and mortality scale with glioblastoma multiforme
(GBM) accounting for almost 80% of all primary tumors of the brain. Despite the increasing availability of
targeted and immunotherapeutic agents, chemotherapy still plays an important role in the treatment of
neoplastic diseases. Limitations to the effective use of chemotherapy such as low aqueous solubility and
high toxicity have directed the scientific community’s interest to the development of new therapeutic
agents with enhanced efficacy and limited toxicity. Supramolecular chemistry has offered an alternative way
on the design and development of new therapeutic agents as a result of their unique properties.
Supramolecules can be used as drug carriers since their cavities can host a wide range of small drugs and
surpass in this way the drawbacks of current therapeutic agents. Herein, we present the principles that
should be followed for the encapsulation of small drugs in supramolecules with enhanced physicochemical
properties and increased efficacy against glioblastoma multiforme.
Key words Glioblastoma multiforme, Temozolomide, Supramolecule, p-sulfonatocalix[4]arene,
Encapsulation,
1
H-NMR spectroscopy, Mass spectrometry, Liquid chromatography, LC-MS/MS
1 Introduction
Cancer is one of the leading global causes of morbidity and mortality. Although targeted and immunotherapeutic agents are increasingly available, systemic chemotherapy continues to have an
important role in the management of the neoplastic disease.
Despite obvious benefits of chemotherapy, its utility is frequently
limited, particularly in metastatic disease, by innate and/or
acquired drug resistance (the latter an inevitable consequence of
tumor heterogeneity) and by toxicity of drugs [1]. Further limitations to the effective use of chemotherapy arise due to poor aqueous solubility, instability, and low drug-loading capacity. The ability