PEG-Modified tert-Octylcalix[8]arenes as Drug Delivery Nanocarriers of Silibinin

Abstract

The hepatoprotective properties of silibinin, as well its therapeutic potential as an anticancer and chemo-preventive agent, have failed to progress towards clinical development and commercialization due to this material’s unfavorable pharmacokinetics and physicochemical properties, low aqueous solubility, and chemical instability. The present contribution is focused on the feasibility of using PEGylated calixarene, in particular polyoxyethylene-derivatized tert-octylcalix[8]arene, to prepare various platforms for the delivery of silibinin, such as inclusion complexes and supramolecular aggregates thereof. The inclusion complex is characterized by various instrumental methods. At concentrations exceeding the critical micellization concentration of PEGylated calixarene, the tremendous solubility increment of silibinin is attributed to the additional solubilization and hydrophobic non-covalent interactions of the drug with supramolecular aggregates. PEG-modified tert-octylcalix[8]arenes, used as drug delivery carriers for silibinin, were additionally investigated for cytotoxicity against human tumor cell lines.

Practical Applications of Supramolecular Macrocyclic Hosts in the Field of Herbal Medicines

“…Drug delivery aims to transport pharmaceuticals to specific targeted sites within the body, with the intention of enhancing , respectively 2022 [104] Silibinin PEG-modified tert-octylcalix [8]arenes Solubility increased by > 1700% 2021 [105] Tanshinone IIA Sulfonated azocalix [4]arene Solubility increased from 0.00194 μg/mL to 1746.7 μg/mL 2023 [106] Thymoquinone CB [7] Solubility clearly enhanced 2022 [107] Sanguinarine Carboxylatopillar [6]arene Solubility increased by 4.3-fold 2017 [108] Camptothecin Pillar [6]arene Solubility increased by 380-fold 2017 [109] 10-hydroxycamptothecin Pillar [6]arene Solubility increased by 40-fold 2017 [109] therapeutic efficacy while minimizing toxic side effects. In recent years, research in the field of drug delivery has flourished with the combination of drug molecules with carriers for the development of targeted nano-vehicles.…”

Applications of supramolecular assemblies in drug delivery and photodynamic therapy

“…103 PEG-modified tert -octylcalix[8]arenes are also used as drug delivery carriers for silibinin and are explored for detecting cytotoxicity against human tumor cell lines. 104…”

“…103 PEG-modified tert-octylcalix [8]arenes are also used as drug delivery carriers for silibinin and are explored for detecting cytotoxicity against human tumor cell lines. 104 The complexation of C4AS with organic guests is dominantly enthalpy driven and would be weakened upon warming. The molecular amphiphilicity of MVC12 can be tuned by either redox or inclusion of CDs.…”

Polymers Enhancing Bioavailability in Drug Delivery

“…Silibinin, a hepatoprotective, anticancer and chemopreventive agent with low aqueous solubility, and chemical instability, has been incorporated in PEG-modified tert-octylcalix[8]arenes, as a drug-delivery platform [ 1 ]. In the first phase, the novel PEGylated polymers were synthesized by the anionic polymerization of ethylene oxide and characterized using diffusion-ordered NMR spectroscopy.…”