Cannabidiol loaded extracellular vesicles sensitize triple-negative breast cancer to doxorubicin in both in-vitro and in vivo models

• Published in: International journal of pharmaceutics 2021-09, Vol.607, p.120943-120943, Article 120943
• Main Authors: Patel, Nilkumar, Kommineni, Nagavendra, Surapaneni, Sunil Kumar, Kalvala, Anil, Yaun, Xuegang, Gebeyehu, Aragaw, Arthur, Peggy, Duke, Leanne C., York, Sara B., Bagde, Arvind, Meckes, David G., Singh, Mandip
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - drug therapy; Cannabidiol; Cell Line, Tumor; Doxorubicin; Doxorubicin and triple negative breast cancer; Extracellular Vesicles; Female; Humans; Sensitization; Triple Negative Breast Neoplasms - drug therapy
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.120943

[Display omitted] •CBD EVs were successfully formulated for the first time with good entrapment efficiency and particle size.•Sustained release of CBD was observed from CBD EVs.•Fluorescent labelled EVs showed rapid intracellular and intratumoral uptake as determined by confocal microscopy.•CBD EVs (5 mg/kg) and DOX combination significantly reduced the tumor burden in MDA-MB-231 xenograft model of athymic nude mice.•CBD EVs sensitized the MDA-MB-231 tumors to DOX by decreasing inflammation, migration, metastasis and facilitating apoptosis. Extracellular Vesicles (EVs) were isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) and were further encapsulated with cannabidiol (CBD) through sonication method (CBD EVs). CBD EVs displayed an average particle size of 114.1 ± 1.02 nm, zeta potential of −30.26 ± 0.12 mV, entrapment efficiency of 92.3 ± 2.21% and stability for several months at 4 °C. CBD release from the EVs was observed as 50.74 ± 2.44% and 53.99 ± 1.4% at pH 6.8 and pH 7.4, respectively after 48 h. Our in-vitro studies demonstrated that CBD either alone or in EVs form significantly sensitized MDA-MB-231 cells to doxorubicin (DOX) (*P