Colloids and Surfaces B: Biointerfaces 143 (2016) 206–212 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces jo ur nal ho me p ag e: www.elsevier.com/locate/colsurfb Development and evaluation of decorated aceclofenac nanocrystals Jeong-Joo Park, Nilesh Meghani, Jin-Seok Choi ∗ , Beom-Jin Lee ∗∗ College of Pharmacy, Ajou University, Suwon-si, Gyounggi-do 443-749, Republic of Korea a r t i c l e i n f o Article history: Received 11 November 2015 Received in revised form 18 February 2016 Accepted 7 March 2016 Available online 10 March 2016 Keywords: Aceclofenac (ACF) Nanocrystals (NC) Solubility Drug release Cell viability a b s t r a c t This study was aimed at achieving enhanced solubility of aceclofenac (ACF) in nanocrystaline forms (ACF-NC) and evaluating the effects of ACF-NC on cell viability. Decorated ACF-NC were prepared by nano-precipitation with stabilizers. Three kinds of stabilizers were investigated: Tween 80, Poloxamer 407, and PEG 6000. The crystal structure and morphology of ACF-NC were characterized by field emission scanning electron microscopy (FE-SEM) and differential scanning calorimetry (DSC). The solubility of ACF- NC and ACF (pure) was evaluated in different media (pH 1.2 and pH 6.8 buffers and distilled water [DW]). A drug release study was performed in PBS for 24 h. Cell viability was evaluated for 24 h using a human colon cancer cell-line (HCT-116) and a human breast cancer cell-line (MCF-7). Decorated ACF-NC with a mean size of 725 nm were successfully prepared. The solubility of the deco- rated ACF-NC were 4–7 times higher than that of ACF in DW and pH 6.8 buffer. A peak shift from 153.1 ◦ C to 150.5–151.0 ◦ C was observed in the DSC thermogram of decorated ACF-NC versus ACF. In terms of drug release, there was an initial burst in decorated ACF-NC within 1 h followed by slow release for up to 4 h. Decorated ACF-NC exhibited viability approximately 63.9% of HCT-116 cells and also showed viability in 58.3% of MCF-7 cells at 15 g/mL of drug concentration. In conclusion, decorated ACF-NC proved to be a promising approach for enhancing drug solubility and cytotoxicity. © 2016 Elsevier B.V. All rights reserved. 1. Introduction According to the Biopharmaceutics Classification System (BCS II), aceclofenac (ACF) is a non-steroidal anti-inflammatory drug (NSAID) with poor water solubility (0.058 g/mL) and high per- meability [1] (Fig. 1). Despite the high permeability of the BCS class II drugs, they often result in low oral bioavailability due to their slow and limited release of drug in gastrointestinal fluid [2]. The market of ACF is limited to Asia, therefore, attempts to develop ACF formulations with high efficacy have to be made in order to expand its market. Approximately 40% of drugs in the development pipelines are poorly soluble in aqueous solvents and some of them in the organic solvents as well [3]. Low aqueous solubility and dissolution rate of API is one of the most prevalent problem that formulation sci- Abbreviations: ACF, aceclofenac; NC, nanocrystals; ACF-NC, aceclofenac nanocrystals; FE-SEM, field emission scanning electron microscopy; DSC, differen- tial scanning calorimetry; DW, distilled water. ∗ Corresponding author at: College of Pharmacy, Ajou University, 206, World cupro, Yeongtong-gu, Suwon-si, Gyenggi-do, 443-749, Republic of Korea. ∗∗ Co-corresponding author. Tel.: +82 31 219 3442; fax: +82 31 212 3653. E-mail addresses: c34281@gmail.com ( J.-S. Choi), beomjinlee@gmail.com (B.-J. Lee). entists are facing, and it is more common among the new drug candidates due to the use of high throughput and combinatorial screening processes during the drug discovery and selection of the new molecular entity (NME) [4,5]. Poorly water-soluble drugs are difficult to develop with commercially available techniques and are frequently abandoned early in the drug development pipeline. The main goal of formulation development for these drugs is to improve solubility. To achieve solubility enhancement, several techniques have been developed, such as solid dispersion [1,6], salt forma- tion [7], co-solvent [8] and particle size reduction (micronization and nanoparticle formation) [9,10]. However, often they cannot solve the bioavailability problem for many drugs. For example, micronization does not create the sufficiently large surface to enhance dissolution rates and therefore, the bioavailability of the many poorly soluble drugs. To overcome the challenge of poor solubility, nanomaterials such as nanocrystals, solid lipid nanoparticles (SLN), nanoemul- sions, and self-assembled nanoparticles have been employed to enhance drug solubilization [11]. Among the various nan- otechniques, drug nanocrystal formulation has been successfully explored for delivery of various anti-cancer drugs [12–15]. Nan- onization of these drug molecules have increased the solubility and dissolution rate owing to increased surface area [16]. Drug nanocrystals ideally exist in a stable crystalline state with high http://dx.doi.org/10.1016/j.colsurfb.2016.03.022 0927-7765/© 2016 Elsevier B.V. All rights reserved.