Co-Loading of Temozolomide and Curcumin into a Calix[4]arene-Based Nanocontainer for Potential Combined Chemotherapy: Binding Features, Enhanced Drug Solubility and Stability in Aqueous Medium.

Rossella Migliore,Carmelo Sgarlata,Nicola D'Antona,Grazia M L Consoli

doi:10.3390/nano11112930

Rossella Migliore, Carmelo Sgarlata + Show 2 more

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https://doi.org/10.3390/nano11112930

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Abstract

The co-delivery of anticancer drugs into tumor cells by a nanocarrier may provide a new paradigm in chemotherapy. Temozolomide and curcumin are anticancer drugs with a synergistic effect in the treatment of multiform glioblastoma. In this study, the entrapment and co-entrapment of temozolomide and curcumin in a p-sulfonato-calix[4]arene nanoparticle was investigated by NMR spectroscopy, UV-vis spectrophotometry, isothermal titration calorimetry, and dynamic light scattering. Critical micellar concentration, nanoparticle size, zeta potential, drug loading percentage, and thermodynamic parameters were all consistent with a drug delivery system. Our data showed that temozolomide is hosted in the cavity of the calix[4]arene building blocks while curcumin is entrapped within the nanoparticle. Isothermal titration calorimetry evidenced that drug complexation and entrapment are entropy driven processes. The loading in the calixarene-based nanocontainer enhanced the solubility and half-life of both drugs, whose medicinal efficacy is affected by low solubility and rapid degradation. The calixarene-based nanocontainer appears to be a promising new candidate for nanocarrier-based drug combination therapy for glioblastoma.

Highlights

The co-vehiculation of drugs by a nanocarrier is currently being investigated as a strategy that might expand successful method that can be used to battle tumors [1]
Basilio et al demonstrated that the amphiphilic SC4OC6 in plain water forms micellar nanoparticles with diameters of 4.27 nm at a critical micellar concentration (CMC) of 0.49 mM [40,41,42]
Since the present study was conducted at neutral pH to simulate biological conditions, we investigated the aggregation features of SC4OC6 in 10 mM phosphate buffer (I = 20 mM) through Isothermal Titration Calorimetry (ITC) measurements

Summary

Introduction

The co-vehiculation of drugs by a nanocarrier is currently being investigated as a strategy that might expand successful method that can be used to battle tumors [1]. By modulating different signaling pathways in cancer cells and causing synergetic responses or additive effects, the combination of two or more drugs can maximize the therapeutic efficacy and overcome tumor drug resistance phenomena [2]. Among the variety of drug mixtures, the combination of temozolomide (TMZ) and curcumin (CUR) has been investigated as a more effective treatment of multiform glioblastoma (GBM), which is the most common and aggressive malignant primary brain tumor that involves various molecular pathways. CUR sensitizes glioblastoma to TMZ treatment [4] and promotes TMZ-induced apoptosis [5] whilst the CUR/TMZ combination

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