Abstract
Systemic toxicity caused by conventional chemotherapy is often regarded as one of the major challenges in the treatment of cancer. Over years, the trigger-based modality has gained much attention as it holds the spatiotemporal control over release and internalization of the drug. In this article, we are reporting an increase in the anti-tumor efficacy of curcumin due to ultrasound pulses. MDA MB 231 breast cancer and B16F10 melanoma cells were incubated with lecithin-based curcumin encapsulated nanoemulsions and exposed to ultrasound in the presence and absence of microbubble. Ultrasound induced sonoporation enhanced the cytotoxicity of curcumin in MDA MB 231 and B16F10 cancer cells in the presence of microbubble by 100- and 64-fold, respectively. To study the spatiotemporal delivery of curcumin, we developed B16F10 melanoma subcutaneous tumor on both the flanks of C57BL/6 mice but only the right tumor was exposed to ultrasound. Insonation of the right tumor spatially enhanced the cytotoxicity and enabled the substantial regression of the right tumor compared to the unexposed left tumor which grew continuously in size. This study showed that the ultrasound has the potential to target and increase the drug’s throughput to the tumor and enable effective treatment.
Highlights
Curcumin is a plant (Curcumin longa) derived anti-inflammatory, antibacterial, antioxidant and anticancer agent with a very minimal side effect
Lin et al found that the IC50 concentration of the cationic liposome-PEG-PEI complex encapsulated curcumin was 1–1.7 μM for a series of cancer cells which was substantially lower than the IC50 concentration (7.9–30 μM) of non-encapsulated curcumin[12]
The zeta potential of the curcumin encapsulated lecithin nanoemulsions (Cur_NE) with different ratio of lecithin and curcumin did not change substantially and was decreasing from −20 to −45 mV (Table 1) which says that particles are stable in the colloidal state in an aqueous medium www.nature.com/scientificreports as the negative zeta potential would substantiate the repulsive forces present between particles and prevent their flocculation[26]
Summary
Curcumin is a plant (Curcumin longa) derived anti-inflammatory, antibacterial, antioxidant and anticancer agent with a very minimal side effect. As only a few nanomolar of curcumin was found in the blood even after the administration of 8 g/day, it is a prerequisite to reduce the IC50 of the drug towards cancer cells to induce effective treatment of tumor. Based on similar rational of using ultrasound responsive microbubbles for cancer therapy, we have combined ultrasound treatment with oral drug delivery of curcumin. We explore the spatiotemporal delivery and anti-tumor activity of the oral curcumin formulation followed by intravenous administration of sulfur hexafluoride (SF6)-containing-lipid-shelled-microbubbles (MB) and ultrasound exposure of the tumor. The oral formulation, curcumin encapsulated lecithin nanoemulsions (Cur_NE) was developed and in vitro cytotoxicity was studied in cancer cells: MDA MB 231 and B16F10. The reduction in volume of the tumor exposed to ultrasound was compared with size reduction in the tumor of the same mice (left tumor) not exposed to ultrasound
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