Characterization of an Amphiphilic Phosphonated Calixarene Carrier Loaded With Carboplatin and Paclitaxel: A Preliminary Study to Treat Colon Cancer in vitro and in vivo

Li, Meiying; Mao, Liujun; Chen, Meirong; Li, Mingxin; Wang, Kaixuan; Mo, Jingxin

doi:10.3389/fbioe.2019.00238

Cited by 26 publications

(11 citation statements)

References 57 publications

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“…On the other hand, testing H/ p -SC6 nanocapsules on HSF noncancer cells confirmed their biocompatibility compared to free harmala seed fraction. The previous studies reported the ability of different host molecules to encapsulate anticancer drugs and selectively deliver them to cancer cells with minimal toxic effects on normal cells. ,,− ,− These results agree with the in vitro release study demonstrating the pH-triggered release of the HARF from the self-assembled H/ p -SC6 nanocapsules. Cancerous cells have an acidic pH of 5.7, normal cells possess a pH of 7.4, whereas late endosomes and lysosomes have pH values of 4.5–5.5.…”

Section: Results and Discussionsupporting

confidence: 86%

Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities

et al. 2021

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Amphiphilic macrocycles, such as p -sulfonatocalix[6]arenes ( p -SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity of various drugs. In the present study, the biologically active harmala alkaloid-rich fraction (HARF) was extracted from Peganum harmala L . seeds. Ultraperformance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC/ESI-MS) analysis of HARF revealed 15 alkaloids. The reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed three peaks: peganine, harmol, and harmine. The HARF was then encapsulated in p -SC6 nanocapsules employing a thin-film hydration approach. The designed nanocapsules had an average particle size of 264.8 ± 10.6 nm, and a surface charge of −30.3 ± 2.2 mV. They were able to encapsulate 89.3 ± 1.4, 74.4 ± 1.3, and 76.1 ± 1.7% of the three harmala alkaloids; harmine, harmol, and peganine; respectively. The in vitro drug release experiments showed the potential of the designed nanocapsules to release their cargo at a pH of 5.5 (typical of cancerous tissue). The IC 50 values of HARF encapsulated in p -SC6 (H/ p -SC6 nanocapsules) were 5 and 2.7 μg/mL against ovarian cancer cells (SKOV-3) and breast adenocarcinoma cells (MCF-7), respectively. The prepared nanocapsules were found to be biocompatible when tested on human skin fibroblasts. Additionally, the antioxidant activity of the designed nanocapsules was 5 times that of the free powder fraction; the IC 50 of the H/ p -SC6 nanocapsules was 30.1 ± 1.3 μg/mL, and that of the HARF was 169.3 ± 7.2 μg/mL. In conclusion, encapsulation of P. harmala alkaloid-rich fraction into self-assembled p -SC6 significantly increases its antioxidant and cytotoxic activities.

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Section: Results and Discussionsupporting

confidence: 86%

Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities

et al. 2021

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“…Another limitation of PTX is its poor solubility in water [ 65 ]. To overcome these problems, various studies demonstrate that efficacy and safety are improved when PTX is encapsulated in calixarene molecules [ 66 , 67 ]. For this purpose, a tetra-hexyloxy- p -sulfonate calix [4] arene (SC4–C6) amphiphilic derivate was synthesized using a thin-film sonication method.…”

Section: Application Of Calixarene On Cancer Therapymentioning

confidence: 99%

“…This formulation mediates a synergistic effect and avoid side effects. The effects of this macro-complex have been studied on human colon cancer cell lines (HT-29 cells and Caco-2 cells) showing greater growth inhibition compared to free drugs [ 67 ]. The combination of carboplatin and paclitaxel was found to be effective for the treatment of ovarian cancer.…”

Section: Application Of Calixarene On Cancer Therapymentioning

confidence: 99%

Role of Calixarene in Chemotherapy Delivery Strategies

et al. 2021

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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.

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“…The use of calixarenes as a macrocyclic component is particularly attractive due to the possibility of modification by various functional groups on both sides of the macrocyclic platform. Moreover, calixarenes are capable of forming complexes with various ions and small organic molecules, which can enter the aromatic cavity of the calixarene framework. − The guest molecules can also be bonded by calixarene substituents located outside the macrocyclic cavity. Sulfonated calix[4]arenes typically form supraamphiphiles with cationic surfactant molecules due to electrostatic interactions. ,,,− The complexation between the surfactant and the macrocycle in this case leads to a decrease in the critical aggregation concentration compared of the individual components.…”

Section: Introductionmentioning

confidence: 99%

“…For example, the attachment of cisplatin to a calixarene scaffold increases anticancer activity . Various macrocyclic compounds are also able to bind platinum preparations into the intramolecular cavity using supramolecular interactions that reduce its toxicity and protect the substance from decomposition. ,− Liposomal − and micellar − cisplatin compositions can also solve the problem of high toxicity. A platinum drug delivery platform was developed using covalent conjugation and coordination-driven self-assembly .…”

Section: Introductionmentioning

confidence: 99%

Supraamphiphilic Systems Based on Metallosurfactant and Calix[4]resorcinol: Self-Assembly and Drug Delivery Potential

et al. 2020

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Metallic amphiphiles are used as building blocks in the construction of nanoscale superstructures, where the hydrophobic effects induce the self-assembly of the nanoparticles of interest. However, the influence of synergizing multiple chemical interactions on an effective design of these structures mostly remains an open question. In this regard, supraamphiphilic systems based on flexible surfactant molecules and rigid macrocycles are being actively developed, but there are few works on the interaction between metallosurfactants and macrocycles. In the present work, the self-assembly and biological properties of a metallosurfactant with calixarene were studied for the first time. The metallosurfactant, a complex between lanthanum nitrate and two 4-aza-1-hexadecylazoniabicyclo[2.2.2]octane bromide units, and calix[4]resorcinol containing sulfonate groups on the upper rim were used to form a novel supraamphiphilic composition. The system formed was studied using a variety of physicochemical methods, including spectrophotometry, NMR, XRF, and dynamic and electrophoretic light scattering. It was found that the most optimal tetraanionic calix[4]resorcinol to dicationic metallosurfactant molar ratio, leading to mixed aggregation upon ion pair complexation, is 2:3. The mixed aggregates formed in the pentamolar concentration range were able to encapsulate hydrophilic substrates, including the anticancer drug cisplatin, the pure form of which is more cytotoxic toward healthy cells than toward diseased cells. Interestingly, the drug loaded into the macrocycle–metallosurfactant particles was less cytotoxic to a healthy Chang liver cell line and more cytotoxic to tumor M-HeLa cells. This selectivity depends on the amount of cisplatin added. The more drug is added to the macrocycle–metallosurfactant composition, the greater the biological activity against cancer cells. Taking into account that the appearance of resistance of cancer cells to drugs, especially to cisplatin, is one of the most important problems in treatment, the results of this work envisage the potential application of a mixed macrocycle–metallosurfactant system for the design of therapeutic cisplatin compositions.

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Characterization of an Amphiphilic Phosphonated Calixarene Carrier Loaded With Carboplatin and Paclitaxel: A Preliminary Study to Treat Colon Cancer in vitro and in vivo

Cited by 26 publications

References 57 publications

Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities

Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities

Role of Calixarene in Chemotherapy Delivery Strategies

Supraamphiphilic Systems Based on Metallosurfactant and Calix[4]resorcinol: Self-Assembly and Drug Delivery Potential

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