In vitro cytotoxicity assay of D-limonene niosomes: an efficient nano-carrier for enhancing solubility of plant-extracted agents

Abstract

The low solubility of the plant-extracted agent like D-limonene in cancer therapy is a critical problem. In this study, we prepared D-limonene-loaded niosomes (D-limonene/Nio) for cancer therapy through in vitro cytotoxicity assay of HepG2, MCF-7, and A549 cell lines. The niosomal formulation was prepared by film hydration technique with Span® 40: Tween® 40: cholesterol (35:35:30 molar ratio) and characterized for vesicle distribution size, morphology, entrapment efficiency (EE%), and in vitro release behaviour. The obtained niosomes showed a nanometric size and spherical morphology with EE% about 87 ± 1.8%. Remarkably prolonged release of D-limonene from niosomes compared to free D-limonene observed. The loaded formulation showed significantly enhanced cytotoxic activity with all three cancer cell lines (HepG2, Macf-7 and A549) at the concentration of 20 μM. These results indicated that niosome loaded with phytochemicals can be a promising nano-carrier for cancer therapy applications

(+)-Limonene 1,2-Epoxide-Loaded SLNs: Evaluation of Drug Release, Antioxidant Activity, and Cytotoxicity in an HaCaT Cell Line

“…The loading of limonene into SLNs decreased cell viability down to 76.27 ± 1.63% (10 µg/mL, at 48 h incubation), while remaining above 70%, which is required to confirm the non-cytotoxic profile. Compared with previous studies [26], in which tumoral cell lines were used, in this study ( Figure 3) the growth inhibition was below 30%, which may indicate a low toxic effect to the non-tumoral cell line HaCaT. The selective effect of (+)-limonene 1,2-epoxide is of interest in several areas of knowledge, deserving further deeper study.…”

“…By plotting the obtained results, a linear regression (y = 4.2026x − 2.644) of R 2 = 0.9902 was obtained and the IC 50 calculated as 207.5 µg/mL. Previous studies have demonstrated the cytotoxicity and anti-tumor activity of (+)-limonene 1,2-epoxide in different cell lines (OVCAR-8, HCT-116, and SF-295), with percentages of growth inhibition varying between 58.48% (SF-295 cells) and 93.10% (OVCAR-8 cells) [26]. We anticipated that the loading of limonene into SLNs could reduce the cytotoxic effect in cells while keeping the antioxidant activity, as shown in Figure 2.…”

“…It is used in the cosmetic industry and perfumery for aromatic purposes, in dermatological applications to induce percutaneous transfer of drugs, and as a sweetener in foodstuffs [25]. Its cytotoxic profile has already been characterized [26], while to exhibit its pharmacological effects, in vitro studies report the need for high concentrations of the terpene.…”

Antioxidant and Anti-Proliferative Activity of Essential Oil and Main Components from Leaves of Aloysia polystachya Harvested in Central Chile

“…The activity is most likely a synergistic effect among the major monoterpenes found in the A. polystachya essential oil [37]. Among the identified terpenes, D-limonene has a demonstrated ability to inhibit cell proliferation, e.g., by inducing apoptosis in lung, stomach, and gastric liver cells [38]. Furthermore, carvone has been shown to be cytotoxic in some tumor cell lines [39,40]; for example, M. spicata oil-with similar carvone content (65.33%)-showed similar cytotoxic activity against the HeLa cell line [41], with IC 50 values below 10 µg/mL.…”

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…At low concentrations, it resulted in production of H 2 O 2 and ERK pathway activation, while at high concentrations it inhibited the farnesylation of proteins and O 2 production [179]. Niosomes containing D-limonene (20 µM) exerted cytotoxic effects on HepG2 and other cell lines [168]. The combination of D-limonene and docetaxel improved the cytotoxicity to DU-145 human prostate carcinoma cells compared to docetaxel alone.…”