Pharmaceutics, Drug Delivery and Pharmaceutical Technology Sustained-Release Curcumin Microparticles for Effective Prophylactic Treatment of Exocrine Dysfunction of Pancreas: A Preclinical Study on Cerulein-Induced Acute Pancreatitis Pratibha Anchi 1 , Amit Khurana 1 , Debasish Swain 2 , Gananadhamu Samanthula 2 , Chandraiah Godugu 1 , * 1 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana 500037, India 2 Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana 500037, India article info Article history: Received 15 March 2018 Revised 13 June 2018 Accepted 5 July 2018 Keywords: acute pancreatitis cerulein curcumin microparticles oxidative stress sustained release abstract Acute pancreatitis (AP) is a serious inflammatory disorder of the pancreas with considerable mortality. The clinical therapy is hampered due to lack of any approved drug for AP. In this study, we developed curcumin (cur)-loaded poly (lactic-co-glycolic acid) cur microparticles (CuMPs) for sustained release. CuMPs were prepared by emulsion solvent evaporation method and characterized for shape, size, compatibility, and entrapment efficiency. The in vitro drug release and in vivo pharmacokinetic studies confirmed sustained release pattern of cur from CuMPs. The pharmacodynamic study was conducted in cerulein induced AP model. Prophylactic treatment was planned with single dose of CuMPs (equivalent to 7.5 mg/kg of cur) and compared with free cur given orally (100 mg/kg) and intraperito- neally (7.5 mg/kg) daily for 7 days. Interestingly, the effects of CuMPs were superior compared to the free drug administered either orally or intraperitoneally through repeated administrations. CuMPs showed significant decrease of serum amylase and lipase levels, oxidative and nitrosative stress was also significantly decreased. Moreover, CuMPs impressively decreased inflammatory cytokines. Our results may pave a way to propose similar strategy for many of promising natural products to combat several oxidative stressemediated disorders via sustained release microparticle approaches. © 2018 American Pharmacists Association ® . Published by Elsevier Inc. All rights reserved. Introduction Pancreas is one of the major secretary organs of the body playing dual roles of an exocrine as well as the endocrine gland. Pancreatic disorders are on all time high number, where considerable morbidity and mortality is ascribed to the dysfunctioning of the exocrine arm of the pancreas. The incidence of acute pancreatitis (AP) has seen a sharp surge in the last decade. 1 The disease is further complicated by the simultaneous multiple organ dysfunction syndrome of lungs, liver, intestine, and kidneys. 2-5 There are no clinically approved drugs to treat patients suffering with AP apart from symptomatic relief with anti-inflammatory agents. Phytoconstituents offer an attractive option to treat oxidoinflammatory disorders like AP. Multiple phy- topharmaceuticals such as curcumin (cur), fisetin, resveratrol, shikonin, and withaferin A have been successfully demonstrated for efficacy in various models of AP. 6 Although preclinically many natural products have shown promising pharmacological effects but the poor bioavailability and other pharmacokinetic (PK) problems hamper their clinical utility and cur is one such molecule. 7-9 Cur, a polyphenolic derivative from the Indian traditional plant Curcuma longa (turmeric), is a proven therapeutic candidate. Cur has been reported effective in disorders of heart, lungs, brain, and so forth. 10-14 Cur exhibits these multiple therapeutic effects by targeting factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) in inflammation, c-Jun N-terminal ki- nases associated signaling pathways and reactive oxygen species (ROS)edependent endoplasmic reticulum stress in cancer, ROS and NF-kB in neurological complications, and mitogen-activated pro- tein kinase (MAPK) in diabetes while in arthritis by tumor necrosis factor-alpha (TNF-a) and mitogen-activated protein kinase/NF-kB modulation. 15 Although possessing diverse therapeutic benefits, cur is still not approved as a therapeutic agent for clinical use. One of the most important reasons is its poor bioavailability due to Conflicts of interest: The authors declare that there are no competent conflicts of interest pertaining to this research work. * Correspondence to: Chandraiah Godugu (Telephone: 040-23073741). E-mail address: chandragodugu@gmail.com (C. Godugu). Contents lists available at ScienceDirect Journal of Pharmaceutical Sciences journal homepage: www.jpharmsci.org https://doi.org/10.1016/j.xphs.2018.07.009 0022-3549/© 2018 American Pharmacists Association ® . Published by Elsevier Inc. All rights reserved. Journal of Pharmaceutical Sciences xxx (2018) 1-14