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

Abstract

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.

Formulation Design, Statistical Optimization, and In Vitro Evaluation of a Naringenin Nanoemulsion to Enhance Apoptotic Activity in A549 Lung Cancer Cells

“…This indicates that the effect of the nanoemulsion on activating apoptosis is related to an increased proportion of cells at the pre-G1 phases and cell arrest at the G2/M phase. Similar findings were observed by others [ 7 , 41 , 42 , 43 ].…”

“…Treatment with NAR-NE produced a significant increase in total apoptotic activity compared with the free NAR treatment (32.16 ± 2.14% versus 0.52 ± 0.17%, respectively; p < 0.05). This difference may result from the low solubility of the naringenin in the culture media, as solubility determines the contact time between the anti-cancer agent and the cancer cells [ 42 , 43 ]. These findings support the potential anti-cancer activity of naringenin and the ability of the nanoemulsion system to enhance its dissolution in vitro.…”

“…Expression of Bax protein induces apoptosis, while expression of Bcl-2 enhances oncogenic/anti-apoptotic activities ( Figure 14 ) [ 40 , 42 ]. Treatment with NAR-NE produced a significant ( p < 0.05) increase in the expression of Bax (351.40 ± 6.31 pg/mL) compared with free NAR (206.20 ± 8.04 pg/mL); this may be explained by the enhancement of dissolution produced by the nanoemulsion.…”

“…Treatment with NAR-NE produced a significant ( p < 0.05) increase in the expression of Bax (351.40 ± 6.31 pg/mL) compared with free NAR (206.20 ± 8.04 pg/mL); this may be explained by the enhancement of dissolution produced by the nanoemulsion. On the other hand, treatment with NAR-NE produced a marked decrease in the expression of Bcl-2 compared with the control, with the effect of the nanoemulsion being greater than that of free naringenin [ 40 , 42 ].…”

Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells

“…Also, formulated nanoparticles induced greater protein expression of Bax and p53 as compared to the individual ITR. The nanoparticles were more efficient in arresting the cells at different cell cycle phases [ 17 ]. The present work aims to develop a delivery vehicle for the synergistic effect of epirubicin and paclitaxel and to evaluate their anticancer potential against the A549 lung cancer cell lines.…”