Curcumin loaded poly(2-hydroxyethyl methacrylate) nanoparticles from gelled ionic liquid – In vitro cytotoxicity and anti-cancer activity in SKOV-3 cells Sathish Sundar Dhilip Kumar a , Surianarayanan Mahadevan a,⇑ , R. Vijayaraghavan b , Asit Baran Mandal a , D.R. MacFarlane b a Thermo Chemical Lab, Chemical Engineering Department, Central Leather Research Institute, Chennai 600 020, India b School of Chemistry, Monash University, Melbourne, Vic. 3800, Australia article info Article history: Received 26 March 2013 Received in revised form 27 August 2013 Accepted 27 August 2013 Available online 5 September 2013 Keywords: Ionic liquids PHEMA Curcumin Nanoparticles Zebrafish SKOV-3 cells abstract The main focus of this study is to encapsulate hydrophobic drug curcumin in hydrophilic polymeric core such as poly(2-hydroxyethyl methacrylate) [PHEMA] nanoparticles from gelled ionic liquid (IL) to improve its efficacy. We have achieved 26.4% drug loading in a biocompatible hydrophilic polymer. Cur- cumin loaded PHEMA nanoparticles (C-PHEMA-NPs) were prepared by nano-precipitation method. Scan- ning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were spherical in shape and free from aggregation. The size and zeta potential of prepared C-PHEMA-NPs were about 300 nm and 33.4 mV respectively. C-PHEMA-NPs were further characterized by FT-IR spectroscopy which confirmed the existence of curcumin in the nanoparticles. X-ray diffraction and differential scanning calorimetry studies revealed that curcumin present in the PHEMA nanoparticles were found to be amorphous in nature. The anticancer activity of C-PHEMA-NPs was measured in ovarian cancer cells (SKOV-3) in vitro, and the results revealed that the C-PHEMA-NPs had better tumor cells regression activity than free curcumin. Flow cytometry showed the significant reduction in G0/G1 cells after treatment with C-PHEMA-NPs and molecular level of apoptosis were also studied using western blotting. Toxicity of PHEMA nanoparticles were studied in zebrafish embryo model and results revealed the material to be highly biocompatible. The present study demonstrates the curcumin loaded PHEMA nanoparticles have potential therapeutic values in the treatment of cancer. Ó 2013 Elsevier B.V. All rights reserved. 1. Introduction Nanoparticles are solid colloidal particles or particulate disper- sions with particle size ranging from 10 to 1000 nm. (Limayem et al., 2004). In recent years, nanoparticle technology has received consideration in improving the effectiveness of drugs. Polymeric nanoparticulate drug delivery systems appear to be feasible and promising. The development of polymeric nanoparticles for targeted delivery and controlled drug release may improve the therapeutic index of drugs (Gu et al., 2008), as they are stable in blood, non-toxic, nonthrombogenic, nonimmunogenic, noninflam- matory, do not activate neutrophils and biodegradable. They also act as carriers for drugs, proteins, peptides, or nucleic acids (Kumari et al., 2010). Recently, a nanoparticle formulation of pac- litaxel [nanometer-sized albumin-bound paclitaxel (Abraxane)], has been applied for the treatment of metastatic breast cancer (Cho et al., 2008). Synthetic polymers have added further interest in this area. Some of these polymers are known for their biocom- patibility and resorbability through natural pathways. Active research is now focused on the preparation of nanoparticles using hydrophilic polymers (Hans and Lowman, 2002; Soppimath et al., 2001). The high degree of surface hydrophilicity will enhance the circulation time of nanoparticles, water solubility and decrease the sensitivity to enzymatic degradation, thereby enhancing bio- compatibility. When exposed to an aqueous environment, the more hydrophilic nanoparticles would degrade easily (Wang et al., 2008; Feng and Chien, 2003). Poly(2-hydroxyethyl methacrylate) [PHEMA] is a synthetic polymer, successfully used in medical applications such as soft contact lenses, drug delivery scaffolds, hydrogels in biomedical engineering, artificial cornea, potential substrate for artificial skin, rhinoplastry, drug delivery systems, and bone composite materials (Oh and Matyjaszewski, 2006; Casadio et al., 2010; Ahmad et al., 2003; Duncan et al., 2001). The presence of polar groups (hydroxyl) and carbonyl on each repeat unit in PHEMA makes this polymer 0928-0987/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejps.2013.08.036 ⇑ Corresponding author. Address: Thermo Chemical Lab, Chemical Engineering Department, Central Leather Research Institute (CLRI), Adyar, Chennai 600 020, Tamilnadu, India. Tel.: +91 44 2491706; fax: +91 44 24911589. E-mail address: msuri1@vsnl.com (M. Surianarayanan). European Journal of Pharmaceutical Sciences 51 (2014) 34–44 Contents lists available at ScienceDirect European Journal of Pharmaceutical Sciences journal homepage: www.elsevier.com/locate/ejps