Abstract
Clinical application of icariin (ICA) is limited, despite its activity against cancer growth, because of the low solubility of ICA in an aqueous environment. Therefore, the present study attempted to develop and optimize ICA-loaded cubosome delivery and to explore its efficacy and possible mechanism of action against ovarian cancer. The optimization of the cubosome formulation was performed using the Box‒Behnken statistical design; during the characterization, the particle sizes were in the range of 73 to 183 nm and the entrapment efficiency was 78.3% to 97.3%. Optimized ICA-loaded cubosomes (ICA-Cubs) exhibited enhanced cytotoxicity and apoptotic potential, compared with ICA-raw, against ovarian cancer cell lines (SKOV-3 and Caov 3). The optimized ICA-Cubs showed a relatively non-cytotoxic effect on normal EA.hy926 endothelial cells. Further analysis of cell cycle arrest suggested a potential role in the pre-G1 and G2/M phases for ICA-Cubs in comparison with ICA-raw. ICA-Cubs increased the generation of reactive oxygen species (ROS) and the overexpression of p53 and caspase-3 in the SKOV-3 cell line. In conclusion, the cubosomal delivery of ICA might provide a prospective approach towards the superior control of ovarian cancer cell growth. Its improved efficacy compared with that of the free drug might be due to the improved solubility and cellular permeability of ICA.
Highlights
IntroductionOf gynecological cancers in women, ovarian cancer is the most common and lethal one, accounting for over 240,000 new cases and 384,000 deaths worldwide in 2018 [1,2]
Of gynecological cancers in women, ovarian cancer is the most common and lethal one, accounting for over 240,000 new cases and 384,000 deaths worldwide in 2018 [1,2].The 5-year survival rate for ovarian cancers varies from 93% when diagnosed at an early stage to 13.4% when diagnosed at an advanced stage [2]
The particle size of nanocarriers plays an important role in cancer therapy because enhanced permeability and intracellular delivery [30]
Summary
Of gynecological cancers in women, ovarian cancer is the most common and lethal one, accounting for over 240,000 new cases and 384,000 deaths worldwide in 2018 [1,2]. The 5-year survival rate for ovarian cancers varies from 93% when diagnosed at an early stage to 13.4% when diagnosed at an advanced stage [2]. Chemotherapy cannot improve the survival rate of patients. Recent studies have been focusing on the effective utilization of natural substances in the treatment of malignancies, and of these, the herbal ones are most investigated [3,4,5,6]. Icariin (ICA, Figure 1) is a flavonol glycoside found in plants, most abundantly in Herba epimedii (Berberidaceae). Previous reports have investigated the regulatory mechanism of ICA in ovarian cancer [7,8]
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