International Journal of Pharmaceutics 456 (2013) 95–100 Contents lists available at ScienceDirect International Journal of Pharmaceutics j o ur nal ho me page: www.elsevier.com/locate/ijpharm Pharmaceutical Nanotechnology Novel cyclodextrin nanosponges for delivery of calcium in hyperphosphatemia Pravin Shende a,b,∗ , Kiran Deshmukh b , Fransesco Trotta a , Fabrizio Caldera a a Department of Chemistry IFM, University of Torino, Via P. Giuria 7, Torino, Italy b Department of Science and Technology of Pharmaceutics, University of Torino, Via P. Giuria 9, Torino, Italy a r t i c l e i n f o Article history: Received 21 June 2013 Received in revised form 5 August 2013 Accepted 10 August 2013 Available online 14 August 2013 Keywords: Nanosponges Calcium carbonate Hyperphosphatemia Phosphate binding a b s t r a c t Cyclodextrin nanosponges are solid, porous nanoparticulate three dimensional structures, have been used as delivery system of different drugs. In this work, new cyclodextrin-based nanosponges of calcium carbonate were prepared by polymer condensation method to release the calcium in controlled manner in the treatment of hyperphosphatemia as novel carriers. SEM measurements revealed their roughly spherical shape, porous nature and mean particle size of about 400 nm. Zeta potentials of the nanosponges were sufficiently high to obtain stable formulations. The encapsulation efficiencies of calcium in nanosponge formulations were found to be 81–95%. The moisture contents of the nanosponges were in the range of 0.1–0.7%. The optimized formulation produces enteric and controlled release kinetics of calcium in the management and treatment of hyperphosphatemia. It was also observed that calcium ions bound efficiently to free phosphate in a pH-dependent fashion especially at pH 7. In accelerated stability study no significant changes occurred in physical appearance, size and nature of drug in formulation for 3 months. The results of FTIR and DSC confirmed that calcium carbonate was encapsulated in nanosponges structure. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Cyclodextrin-based nanosponges are biocompatible nanoporous nanoparticles (Cavalli et al., 2010), used to increase the dissolution rate, solubility and stability of drugs (Swaminathan et al., 2010), to mask unpleasant flavors, to convert liquid sub- stances to solids and to prolong the release of drug (Trotta, 2011). Mostly two methods used for the preparation of nanosponges viz. cross-linking reaction by condensation polymerization (Trotta and Tumiatti, 2003) and cross-linking reaction by interfacial phenomenon (Trotta et al., 2012a). Nanosponges prepared by poly- merization reaction showed the promising results in anticancer drug delivery system, proteins delivery system, anti-inflammatory drugs delivery system etc. (Shende et al., 2012). Calcium carbonate is most widely used as calcium source and least expensive dietary supplement for calcium. It is absorbed through intestine, calcium and carbonate ions come in normal metabolic pathways and body pools. The major part of absorbed calcium is accumulated in the skeleton. Excess calcium is excreted with water via kidneys, feces and skin; and excess carbonate is excreted as carbon dioxide via respiration (www.efsa.europa.eu). ∗ Corresponding author at: Department of Chemistry IFM, University of Torino, Via Pietro Giuria 7, Torino 10125, Italy. E-mail address: shendepravin94@gmail.com (P. Shende). Calcium carbonate is also used in the management of hyper- phosphatemia in renal failure and also as an antacid, in the treatment of osteoporosis (Zamfirescu and Carlson, 2011). Herein we intended and extended nanosponges applications for intes- tine specific delivery of calcium in hyperphosphatemia treatment. Hyperphosphatemia can be caused by hypoparathyroidism due to the lack of parathyroid hormone, which has the effect of inhibiting renal reabsorption of phosphate. Commercially available phosphate binders for treatment of hyperphosphatemia produce toxicity like bone disease and aluminum dementia from aluminum- containing antacids and hypercalcemia and soft tissue calcification from calcium-containing antacids (Ranganathan, 2012). So, the aim of the work was to formulate and characterize enteric-coated, controlled-release calcium carbonate nanosponges to bind effi- ciently free phosphate ions to treat the hyperphosphatemia. 2. Materials and methods 2.1. Materials ˇ-Cyclodextrin was a kind gift from Roquette Italia (Cas- sano Spinola, Italy). 1,1 ′ -Carbonyl diimidazole, calcium carbonate, dimethyl formamide (DMF), potassium dihydrogen phosphate and ethanol were purchased from Sigma Aldrich, Germany. Phosphate assay kits were purchased from Bioassay, USA. All other chemicals were used of analytical grades. 0378-5173/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijpharm.2013.08.012