Azadiradione-Loaded Liposomes with Improved Bioavailability and Anticancer Efficacy Against Triple Negative Breast Cancer

Abstract

Triple negative breast cancer (TNBC) is the most aggressive subtype of the breast cancer commonly occurring in females. It was estimated that around 17%–25% of people with breast cancer are triple negative. Despite the availability of various therapeutics and approaches for breast cancer treatment, there is still an increasing need to develop safe and efficacious agents for cancer therapy. Azadiradione (AZD), a bioactive agent isolated from Azadiractaindica, is known to possess anti-nociceptive and anti-inflammatory activities. However, AZD use is limited due to its poor bioavailability. In the current study, the bioavailability of AZD-loaded liposomes in mice was investigated. The anticancer efficacy of AZD-loaded liposomes against TNBC cell line (MDA-MB-231) was also assessed. Data have shown that the oral bioavailability of AZD from liposomes was significantly higher in comparison to free AZD. Also, the anticancer activity of AZD-loaded liposomes against TNBC cells in vitro was markedly enhanced and was found to be via down regulation of the proteins required for proliferation, survival and angiogenesis such as cyclin D1, COX-2, survivin, VEGF-A and autophagy. In conclusion, this study suggested that AZD-loaded liposomes might be a potential oral delivery system to improve bioavailability and hence, therapeutic efficacy of AZD. However, further surface modification of AZD liposomes via PEGylation is required to increase drug blood circulation and reduce phagocytosis and uptake by RES.