Pharmaceutics, Drug Delivery and Pharmaceutical Technology Thai Silk Fibroin/Gelatin Sponges for the Dual Controlled Release of Curcumin and Docosahexaenoic Acid for Anticancer Treatment Kantarat Lerdchai 1 , Jutarat Kitsongsermthon 2 , Juthamas Ratanavaraporn 3 , Sorada Kanokpanont 1 , Siriporn Damrongsakkul 1 , * 1 Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, PhayaThai Road, Bangkok 10330, Thailand 2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, PhayaThai Road, Bangkok 10330, Thailand 3 Biomedical Engineering Program, Faculty of Engineering, Chulalongkorn University, PhayaThai Road, Bangkok 10330, Thailand article info Article history: Received 11 June 2015 Revised 31 July 2015 Accepted 30 September 2015 Available online 18 November 2015 Keywords: silk fibroin gelatin curcumin DHA cervical cancer cells controlled release cell culture biodegradable polymers proteins toxicology abstract In this study, curcumin and/or docosahexaenoic acid (DHA) were encapsulated in Thai silk fibroin/gelatin (SF/G) sponges, prepared at different blending ratios, aimed to be applied as a controlled release system for localized cancer therapy. The SF/G sponges were fabricated by freeze-drying and glutaraldehyde cross-linking techniques. Physicochemical properties of the SF/G sponges were characterized. Then, curcumin and/or DHA were loaded in the sponges by physical adsorption. The encapsulation efficiency and the in vitro release of curcumin and/or DHA from the sponges were evaluated. SF/G sponges could encapsulate curcumin and/or DHA at high encapsulation efficiency. The highly cross-linked and slowly degrading SF/G (50/50) sponge released curcumin and/or DHA at the slowest rate. The in vitro cyto- toxicity of the sponges against noncancer cells (L929 mouse fibroblast) and anticancer of curcumin and/ or DHA released from the sponges against cervical cancer cells (CaSki) were tested. All sponges were not toxic to L929 mouse fibroblast. The mixed curcumineDHA at the ratio of 1:4 had the highest inhibiting effect on the growth of CaSki, comparing with the release of curcumin or DHA alone. SF/G sponges could be a potential carrier for dual release of curcumin and DHA for anticancer effect. © 2016 American Pharmacists Association ® . Published by Elsevier Inc. All rights reserved. Introduction Cancer has currently become one of the most intimidating dis- eases in which millions of people worldwide are suffering from. Cervical cancer is the second most cancer causing women's death. In 2012, the statistics showed that over 265,000 women were dead from cervical cancer. 1 The standard treatments of cervical cancer include surgery, radiotherapy, and chemotherapy with cisplatin, carboplatin, paclitaxel and so on. 2,3 For chemotherapy method, high dose of drugs is required to kill cancer cells. Unfortunately, these drugs also have high toxicity to normal cells and usually bring some adverse side effects such as immune suppression, sore mouth, and hair loss. 3 To avoid or reduce these effects, the natural- derived compounds that have anticancer activity may be a prom- ising choice to be applied instead of or along with the lower dose of chemotherapeutic drugs. Curcumin is a yellow hydrophobic polyphenolic compound extracted from the rhizome of turmeric (Curcuma longa). It is reported to be an antiinflammatory, antioxidant, and anticancer activities. 4,5 Curcumin showed therapeutic potential against various cancers including leukemia, gastrointestinal cancers, breast cancer, ovarian cancer, lung cancer, and cervical cancer. 4,6 A number of studies revealed that curcumin inhibits cancer growth by suppressing proinflammatory pathways and angiogenesis, resulting in the apoptosis of cancer cells. 5,7,8 Curcumin also acts as an antioxidant for cancer chemoprevention. 7 The clinical trial has established that oral administration of curcumin even at high dose (8-12 g/day) was safe. 9 However, the disadvantages of curucmin are poor systematic bioavailability because of its poor solubility in water, rapid metabolism, and short half-life. 9,10 Therefore, the controlled release system for curcumin is required in order to reduce dose of drug, enhance drug's bioavailability and stability, Abbreviations used: CaSki, cervical cancer cells; DHA, docosahexaenoic acid; DMEM, Dulbecco's modified Eagle powder medium; DMSO, dimethyl sulfoxide; G, gelatin; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS, phosphate-buffered saline; SF, silk fibroin. * Correspondence to: Siriporn Damrongsakkul (Telephone: þ662-218-6862; Fax: þ662-218-6877). E-mail address: siriporn.d@chula.ac.th (S. Damrongsakkul). Contents lists available at ScienceDirect Journal of Pharmaceutical Sciences journal homepage: www.jpharmsci.org http://dx.doi.org/10.1002/jps.24701 0022-3549/© 2016 American Pharmacists Association ® . Published by Elsevier Inc. All rights reserved. Journal of Pharmaceutical Sciences 105 (2016) 221e230