Role of Calixarene in Chemotherapy Delivery Strategies

Abstract

Since cancer is a multifactorial disease with a high mortality rate, the study of new therapeutic strategies is one of the main objectives in modern research. Numerous chemotherapeutic agents, although widely used, have the disadvantage of being not very soluble in water or selective towards cancerous cells, with consequent side effects. Therefore, in recent years, a greater interest has emerged in innovative drug delivery systems (DDSs) such as calixarene, a third-generation supramolecular compound. Calixarene and its water-soluble derivatives show good biocompatibility and have low cytotoxicity. Thanks to their chemical–physical characteristics, calixarenes can be easily functionalized, and by itself can encapsulate host molecules forming nanostructures capable of releasing drugs in a controlled way. The encapsulation of anticancer drugs in a calixarene derivate improves their bioavailability and efficacy. Thus, the use of calixarenes as carriers of anticancer drugs could reduce their side effects and increase their affinity towards the target. This review summarizes the numerous research advances regarding the development of calixarene nanoparticles capable of encapsulating various anticancer drugs.

PAMAM-calix-dendrimers: Synthesis and Thiacalixarene Conformation Effect on DNA Binding

“…(Thia)calixarene scaffold is non-toxic. It is known that the covalent binding of various toxic molecules with (thia)calixarene scaffold decreases their toxicity [ 20 , 21 ]. The possibility of easy synthesis of stereoisomers with different spatial arrangements of substituents is another advantage of the thiacalixarene platform.…”

Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin

“…Supramolecular host molecules, comprising calix[n]arenes (CXs), cyclodextrins (CDs), cucurbiturils (CBs), and pillararenes, have been suggested as smart drug delivery platforms [1,22,23] and have been used as host molecules to encapsulate various chemotherapeutic drugs to improve their bioavailability, prevent their premature degradation in the bloodstream, and increase their targeted intracellular uptake into cancer cells [1][2][3]. Lately, calix[n]arenes (n = 4, 6, and 8) have been employed in drug targeting [24][25][26]. Calixarenes are idyllic host molecules that are synthesized by linking phenolic rings via methylene bridges encompassing three regions; (1) a lower rim with a phenolic hydroxyl group, (2) an upper rim with a para-substituent of a phenolic unit, and (3) a hydrophobic π electron-rich central cavity.…”

Insight into the Inclusion Complexation of Fluconazole with Sulfonatocalix[4]naphthalene in Aqueous Solution, Solid-State, and Its Antimycotic Activity

“…Furthermore, calix[n]arenes exhibited better compatibility and decreased toxicity than naturally occurring macrocyclic CD's, and their fast and easy synthesis method could be adapted for large-scale production [18,19]. For these advantages, the potential application of calix [n]arenes is reported to enhance the bioavailability and water solubility of different drugs such as oxaliplatin [20], doxorubicin [21], isoniazid ciprofloxacin [22], tenofovir disoproxil fumarate [23], carbamazepine [14], nifedipine [14,24], and niclosamide [14,24]. The sulfonatocalix [4]naphthalene macrocycle has unique properties, such as higher water solubility and large cavity size compared with CD's and p-sulfonatocalix[n]arene macrocycles (Figure 1, compound 2) [25][26][27][28].…”