Repurposing itraconazole to the benefit of skin cancer treatment: A combined azole-DDAB nanoencapsulation strategy

Carbone, Claudia; Martins-Gomes, Carlos; Pepe, Veronica; Silva, Amélia M.; Musumeci, Teresa; Puglisi, Giovanni; Furneri, Pio Maria; Souto, Eliana B.

doi:10.1016/j.colsurfb.2018.04.031

Cited by 35 publications

(12 citation statements)

References 35 publications

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“…The enhanced efficacy of itraconazole against human glioblastoma cancer cell lines by its incorporation into solid lipid nanoparticles with a coating layer of cationic lipid was reported previously [2]. Several platforms of nanoparticulates have been examined and formulated for the delivery of numerous drugs.…”

Section: Introductionmentioning

confidence: 93%

“…Itraconazole, a broad-spectrum, poorly water-soluble, and antifungal drug is ordinarily used for treating superficial infections caused by dermatophytes. The drug is active against a broad range of fungal infections, and is especially active against histoplasmosis, blastomycosis, Aspergillus app., and sporotrichosis [2]. Itraconazole's anticancer effects include inhibition of angiogenesis, as well as other mechanisms, including inhibition of hedgehog signaling [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers

Alhakamy

Shadab

2019

Pharmaceutics

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Itraconazole (ITR) is a broad-spectrum antifungal drug, which has been shown to possess some promising anticancer, anti-proliferative, and anti-angiogenic properties in some cancers, such as cancers of the lung, breast, and skin. However, ITR has some drawbacks, such as poor water solubility, which hinder its use as a therapeutic agent. Therefore, in the present study, we developed and characterized chitosan-coated PLGA nanoparticles of itraconazole and studied their anticancer activities in H1299 lung cancer cells. The prepared ITR nanoparticles showed a small particle size, narrow poly dispersity index (PDI), positive zeta potential, and a controlled drug release profile. The cytotoxicity of ITR nanoparticles (NPs) on H1299 cancer cells after 24 h of exposure was greater than that of the ITR solution. Apoptosis of cancer cells exposed to ITR nanoparticles was also enhanced in comparison with the ITR solution. At the molecular level, ITR NPs were more effective than ITR solution in inducing pro-apoptotic Bax and p53 while reducing anti-apoptotic Bcl2 protein expression. ITR NPs were more effective than ITR solution in arresting cells both at the G0/G1 as well as G2/M phases of the cell cycle. Hence, repurposing itraconazole by encapsulation into PLGA NPs with chitosan coating is a potentially promising approach to treat lung cancers.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers

Alhakamy

Shadab

2019

Pharmaceutics

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“…These properties are usually assessed by several methods, aiming for the full characterization of the NPs. Electron microscopy, dynamic light scattering (DLS) or photon correlation spectroscopy (PCS), Near-infrared spectroscopy, electrophoresis, and chromatography are a few of the most commonly used [59,60]. Polymeric NPs characterization is very important, in terms of its applicability, but also to ascertain issues concerning nanotoxicology and exposure assessment in workplaces, which are important to assess their health and safety hazards, as well as to control manufacturing processes [61].…”

Section: Characterization Of Polymeric Nanoparticlesmentioning

confidence: 99%

Polymeric Nanoparticles: Production, Characterization, Toxicology and Ecotoxicology

et al. 2020

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Polymeric nanoparticles (NPs) are particles within the size range from 1 to 1000 nm and can be loaded with active compounds entrapped within or surface-adsorbed onto the polymeric core. The term “nanoparticle” stands for both nanocapsules and nanospheres, which are distinguished by the morphological structure. Polymeric NPs have shown great potential for targeted delivery of drugs for the treatment of several diseases. In this review, we discuss the most commonly used methods for the production and characterization of polymeric NPs, the association efficiency of the active compound to the polymeric core, and the in vitro release mechanisms. As the safety of nanoparticles is a high priority, we also discuss the toxicology and ecotoxicology of nanoparticles to humans and to the environment.

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“…SK-MEL-5 is a human melanoma cell line derived from a metastatic axillary node of a young female patient, and is characterized by a high level of expression of the V600E mutation of BRAF and the wild-type NRAS [1], as well as by relatively high levels of the ABCB1 transcript [2]. It has been used in various studies to explore new therapies against melanoma in various in vitro experiments [3,4]. Several potent drugs are now available in clinical trials against melanoma including kinase inhibitors with different degree of success.…”

Section: Introductionmentioning

confidence: 99%

Design of potential anti-melanoma agents against SK-MEL-5 cell line using QSAR modeling and molecular docking methods

2020

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SK-MEL-5 is a human melanoma cell line that has been used in several researches to explore new therapies against melanoma. Based on this study we report on the development of quantitative structure-activity relationship (QSAR) model and molecular docking simulation able to predict the cytotoxic effect of diverse chemical compounds on this cancer cell line. The dataset of seventy-two (72) cytotoxic compounds were downloaded from the National Cancer Institute database. It contains the data of compounds for which cytotoxicity results expressed by pGI 50 was recorded. The QSAR model was built using fifty (50) compounds and the best-generated model based on multiple linear regression showed, respectively good quality of fits [ R 2 (0.864), R 2 adjusted (0.846), Q 2 cv (0.841) and R 2 pred (0.885)]. The model's predictive ability was determined by a test set of twenty-two (22) compounds and the applicability domain was assessed through leveraged approach. Compounds 41 and 69 were selected as templates for in silico design because they had high pGI 50 activity and are within the model's applicability domain. The obtained information from the model was explored to design novel compounds by introducing various substituents. Moreover, the designed compounds were docked into the active site of the protein (PDB CODE: 3OG7) which is responsible for melanoma cancer to elucidate their binding mode. Ia (− 12.4 kcal mol −1) and IIb (− 12.3 kcal mol −1) showed a better binding affinity for the target when compared with (vemurafenib, − 11.3 kcal mol −1) the known inhibitor of the target (V600E-BRAF). These results may be of great help in early anticancer drug discovery.

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Repurposing itraconazole to the benefit of skin cancer treatment: A combined azole-DDAB nanoencapsulation strategy

Cited by 35 publications

References 35 publications

Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers

Repurposing Itraconazole Loaded PLGA Nanoparticles for Improved Antitumor Efficacy in Non-Small Cell Lung Cancers

Polymeric Nanoparticles: Production, Characterization, Toxicology and Ecotoxicology

Design of potential anti-melanoma agents against SK-MEL-5 cell line using QSAR modeling and molecular docking methods

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