Research Article Plumbagin-Loaded Nanoemulsion Drug Delivery Formulation and Evaluation of Antiproliferative Effect on Prostate Cancer Cells Adrian Chrastina , Veronique T. Baron, Parisa Abedinpour, Gaelle Rondeau, John Welsh, and Per Borgström Vaccine Research Institute of San Diego (VRISD), San Diego Science Center, San Diego, California, USA Correspondence should be addressed to Adrian Chrastina; achrastina@vrisd.org Received 12 June 2018; Revised 19 September 2018; Accepted 24 October 2018; Published 11 November 2018 Guest Editor: Claudio Tabolacci Copyright © 2018 Adrian Chrastina et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Plumbagin, a medicinal plant-derived 5-hydroxy-2-methyl-1,4-naphthoquinone, is an emerging drug with a variety of pharmacological efects, including potent anticancer activity. We have previously shown that plumbagin improves the efcacy of androgen deprivation therapy (ADT) in prostate cancer and it is now being evaluated in phase I clinical trial. However, the development of formulation of plumbagin as a compound with sparing solubility in water is challenging. Methods. We have formulated plumbagin-loaded nanoemulsion using pneumatically controlled high pressure homogenization of oleic acid dispersions with polyoxyethylene (20) sorbitan monooleate as surfactant. Nanoemulsion formulations were characterized for particle size distribution by dynamic light scattering (DLS). Te kinetics of in vitro drug release was determined by equilibrium dialysis. Anticancer activity toward prostate cancer cells PTEN-P2 was assessed by MTS (Owen’s reagent) assay. Results. Particle size distribution of nanoemulsions is tunable and depends on the surfactant concentration. Nanoemulsion formulations of plumbagin with 1-3.5% (w/w) of surfactant showed robust stability of size distribution over time. Plumbagin-loaded nanoemulsion with average hydrodynamic diameter of 135 nm showed exponential release of plumbagin with a half-life of 6.1 h in simulated gastric fuid, 7.0 h in simulated intestinal fuid, and displayed enhanced antiproliferative efect toward prostate cancer cells PTEN-P2 compared to free plumbagin. Conclusion. High drug-loading capacity, retention of nanoparticle size, kinetics of release under simulated physiological conditions, and increased antiproliferative activity indicate that oleic-acid based nanoemulsion formulation is a suitable delivery system of plumbagin. 1. Introduction Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, Fig- ure 1) is a plant-derived secondary metabolite found in plant families such as Plumbaginaceae, Ebenaceae, Dioncophyl- laceae, Ancestrocladaceae, and Droseraceae [1]. Plumbagin possesses multiple pharmacological activities, such as anti- cancer, antiatherosclerotic, antidiabetic, anti-infammatory, antimicrobial, hypolipidemic, and neuroprotective activities [2, 3]. Recently, signifcant research efort was developed to evaluate antitumor efects of plumbagin. Plumbagin showed potent anti-tumor activity in various tumor mod- els, including breast cancer [4], Ehrlich ascites carcinoma [5], esophageal cancer [6], lung cancer [7], melanoma [8], ovarian cancer [9], promyelocytic leukemia [10], and prostate cancer [11–13]. Plumbagin exhibits these anticancer efects via interaction with multiple targets and modulation of various molecular signaling pathways, including AMPK, CDK1/CDC2, cyclin B1, cyclin D1, NF-kappaB, p53, p21 Waf1/Cip1, p27 Kip1, Nrf2/ARE, PI3K/AKT/mTOR, Ras, STAT3/PLK1/AKT, and Wnt [3], resulting in induction of apoptosis and autophagy, cell cycle arrest, inhibition of invasion, and metastasis, as well as antiangiogenic activities [2]. Great progress has recently been made regarding its use in prostate cancer. For example, experiments from Dr. Verma’s laboratory demonstrated that plumbagin administered by intraperitoneal injection strongly inhibited tumor growth Hindawi BioMed Research International Volume 2018, Article ID 9035452, 7 pages https://doi.org/10.1155/2018/9035452