199
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_16,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 16
Antitumor Efficacy of Ceranib-2 with Nano-Formulation
of PEG and Rosin Esters
Ali Ben Taleb, Selcan Karakuş, Ezgi Tan, Merve Ilgar, Özlem Kutlu,
Devrim Gözüaçık, Hatice Mehtap Kutlu, and Ayben Kilislioğlu
Abstract
Ceranib-2 is a recently discovered, poorly water-soluble potent ceramidase inhibitor, with the ability to
suppress cancer cell proliferation and delay tumor growth. However, its poor water solubility and weak
cellular bioavailability hinder its use as a therapeutic agent for cancer. PEGylated rosin esters are an excellent platform as a natural polymer for drug delivery applications, especially for controlling drug release due
to their degradability, biocompatibility, capability to improve solubility, and pharmacokinetics of potent
drugs. In this study, stable aqueous amphiphilic submicron-sized PEG400-rosin ester-ceranib-2 (PREC-2)
particles, ranging between 100 and 350 nm in a 1:1 mixture, were successfully synthesized by solvent
evaporation mediated by sonication.
Conclusion: Stable aqueous PEGylated rosin ester nanocarriers might present a significant solution to
improve solubility, pharmacokinetic, and bioavailability of ceranib-2, and hold promises for use as an anticancer adjacent drug after further investigations.
Key words Ceranib-2, Rosin ester, PEGylation, Nanoencapsulation, Anticancer
1 Introduction
Cancers are a major public healthcare problem worldwide and the
second leading cause of death in Europe and North America [1,
2]. The International Agency for Research on Cancer (IARC)
reported that the global cancer burden is estimated to rise to 21.5
million new cases and 11.500 million deaths by 2025 [3, 4].
Recently, significant success has been made in developing new
safe, less toxic anticancer drugs. Nonetheless, despite these successes, many newly discovered potent anticancer agents fail to be
developed as promising clinical anticancer drugs due to several
physiochemical and biological reasons [5]. Therefore, efforts are
ongoing to identify novel efficient nonconventional drug delivery
system to achieve optimum therapeutic effects with minimal side
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_16,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 16
Antitumor Efficacy of Ceranib-2 with Nano-Formulation
of PEG and Rosin Esters
Ali Ben Taleb, Selcan Karakuş, Ezgi Tan, Merve Ilgar, Özlem Kutlu,
Devrim Gözüaçık, Hatice Mehtap Kutlu, and Ayben Kilislioğlu
Abstract
Ceranib-2 is a recently discovered, poorly water-soluble potent ceramidase inhibitor, with the ability to
suppress cancer cell proliferation and delay tumor growth. However, its poor water solubility and weak
cellular bioavailability hinder its use as a therapeutic agent for cancer. PEGylated rosin esters are an excellent platform as a natural polymer for drug delivery applications, especially for controlling drug release due
to their degradability, biocompatibility, capability to improve solubility, and pharmacokinetics of potent
drugs. In this study, stable aqueous amphiphilic submicron-sized PEG400-rosin ester-ceranib-2 (PREC-2)
particles, ranging between 100 and 350 nm in a 1:1 mixture, were successfully synthesized by solvent
evaporation mediated by sonication.
Conclusion: Stable aqueous PEGylated rosin ester nanocarriers might present a significant solution to
improve solubility, pharmacokinetic, and bioavailability of ceranib-2, and hold promises for use as an anticancer adjacent drug after further investigations.
Key words Ceranib-2, Rosin ester, PEGylation, Nanoencapsulation, Anticancer
1 Introduction
Cancers are a major public healthcare problem worldwide and the
second leading cause of death in Europe and North America [1,
2]. The International Agency for Research on Cancer (IARC)
reported that the global cancer burden is estimated to rise to 21.5
million new cases and 11.500 million deaths by 2025 [3, 4].
Recently, significant success has been made in developing new
safe, less toxic anticancer drugs. Nonetheless, despite these successes, many newly discovered potent anticancer agents fail to be
developed as promising clinical anticancer drugs due to several
physiochemical and biological reasons [5]. Therefore, efforts are
ongoing to identify novel efficient nonconventional drug delivery
system to achieve optimum therapeutic effects with minimal side