Remedy Publications LLC., | http://clinicsinoncology.com/ Clinics in Oncology 2021 | Volume 6 | Article 1769 1 Bovine Milk Derived Exosomal - Curcumin Exhibiting Enhanced Stability, Solubility, and Cellular Bioavailability OPEN ACCESS *Correspondence: Manda Sasidhar Venkata, Apollo Hospital Educational and Research Foundation, AIMSR Building 1st Floor, Apollo Health Street Apollo Hospitals, Jubilee Hills, Hyderabad - 96, India, Tel: 040-29551071; Fax: 91-40-23543270; E-mail: sasidhar@aherf.net Received Date: 11 Jan 2021 Accepted Date: 04 Feb 2021 Published Date: 08 Feb 2021 Citation: Singh AD, Sreenu B, Alvi SB, Patnam S, Rajeswari K, Kutala VK, et al. Bovine Milk Derived Exosomal - Curcumin Exhibiting Enhanced Stability, Solubility, and Cellular Bioavailability. Clin Oncol. 2021; 6: 1769. Copyright © 2021 Manda Sasidhar Venkata. This 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. Research Article Published: 08 Feb, 2021 Abstract Curcumin is a promising anti-cancer drug with limited aqueous solubility and decreased bioavailability. Milk Extracellular Vesicles (MEVs) used as a drug-delivery vehicle, were precipitated with Poly-Ethylene-Glycol (PEG) MW3000 from milk-whey. Te yield of MEVs was 200.0 ± 0.85 mg/liter of whey. MEVs were spherical, double-membrane structures with a size range of 92 ± 30 nm/Nanoparticle-Tracking-Analysis (NTA) and 87 ± 40 nm/Dynamic-Light Scattering (DLS). A 70% loading efciency was achieved with a passive loading of curcumin. Te mean size of mev- curcumin was 152 ± 49 nm/NTA and 113 ± 67 nm/DLS. A six-fold increase of cytotoxicity and a two fold increase in curcumin accumulation were observed by mev-curcumin over native curcumin in MDA-MB231, a breast cancer cell-line. Tus, we report the development of a curcumin formulation with improved solubility, stability, and cellular permeability for breast-cancer treatments. Anula Divyash Singh 1,3 , Sreenu B 2 , Syed Baseeruddin Alvi 3 , Sreekanth Patnam 1,3 , Rajeswari K 1 , Vijay Kumar Kutala 2 , Aravind Kumar Rengan 3 and Manda Sasidhar Venkata 1,4 * 1 Apollo Hospitals Educational and Research Foundation (AHERF), India 2 Nizam's Institute of Medical Sciences, Hyderabad, India (NIMS), India 3 Department of Biomedical Engineering, Indian Institute of Technology Hyderabad (IITH), India 4 Urvogelbio Private Ltd, India Abbreviations Cur: Curcumin; DLS: Dynamic Light Scattering; GAPDH: Glyceraldehyde 3-Phosphate Dehydrogenase; Mev: Milk extracellular vesicle or bovine EV; Mev-curcumin: Milk exosomal curcumin; NTA: Nanoparticle Tracking Analysis; TEM: Transmission Electron Microscope Introduction Breast Cancer (BC) is the most common cancer in women with increased morbidity and mortality globally. BC's standard treatment includes surgery, chemotherapy, hormonal therapy, and radiotherapy, and the choice of treatment is arrived based on its clinical and histopathological features [1,2]. However, treatment resistance quickly sets in as the disease progresses in almost 30% of BC patients. Novel therapeutic options, including curcumin, were investigated as a potential therapeutic for treating BC [2-5]. Curcumin is an active phenolic compound isolated from Curcuma longa [6]. Curcumin has diferuloylmethane, dimethoxy-curcumin, and bisdemethoxycurcumin in a ratio of 77:17:6 [7]. It exhibits anti-proliferative, antioxidant, anti-infammatory, and anti-cancer properties [8- 12]. Curcumin has been shown to inhibit migration, invasion, and apoptosis of various cancers, including BC [8]. Curcumin's clinical utility has been limited due to its low aqueous solubility and stability, leading to low bioavailability [13]. Improved curcumin stability is achieved with diferent approaches, including structure modifcation and reformulation with nanotechnology- based strategies [14,15]. However, no developed curcumin formulation exhibited the required drug stability, improved aqueous solubility, increased bioavailability, and proper tissue distribution. MDA-MB-231 is an aggressive triple-negative breast cancer cell line commonly used to develop and test novel therapeutic approaches in BC [1]. Extracellular Vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are membrane vesicles found in all biological fuids, including milk [16]. EVs play a signifcant role in contributing to cellular homeostasis. Teir endogenous cellular origin results in increased biocompatibility and limited immunogenicity, making them ideal candidates as a drug delivery vehicle. EVs have been used to deliver drugs, proteins, siRNAs, miRNAs, etc. EVs can be further bioengineered to enhance their penetrance and targetability [17]. However, the lack of optimized isolation protocols and lack of cheaper source material for EVs purifcation severely hampered the