Novel core-corona hybrid nanomaterials based on the conjugation of amphiphilic polymeric diblocks to the surface of multifunctional nanodiamond anchors Doaa Abu Saleh a , Olga Shimoni b , Alejandro Sosnik a, * a Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion-Israel Institute of Technology, Haifa, Israel b School of Mathematical and Physical Sciences, University of Technology Sydney (UTS), Ultimo, New South Wales, Australia article info Article history: Received 20 October 2016 Received in revised form 15 December 2016 Accepted 16 December 2016 abstract The poor aqueous solubility and the physicochemical instability of many marketed drugs and new chemical entities is one of the most challenging issues in pharmaceutical research and development. Polymeric micelles (PMs) are produced by the self-assembly of polymeric amphiphiles and they repre- sent one of the most extensively investigated nanotechnology platforms for encapsulation, delivery and targeting of hydrophobic drugs. However, a main challenge is preventing their disassembly under extreme dilution in the body fluids, which leads to uncontrolled release of the encapsulated cargo. In this work, we developed an amphiphilic nanomaterial that resembles the core-corona architecture of a PM with superior stability in the body fluids. Specifically, we utilized carboxylated nanodiamonds (cNDs) as particulate anchors to covalently link amphiphilic diblock copolymers consisting of poly(epsilon- caprolactone) (PCL) and poly(ethylene glycol) monomethyl ether (PEG) as hydrophobic and hydrophil- ic components, respectively. We confirmed a successful core-corona nanostructure using various char- acterization techniques. In addition, TEM revealed the presence of a thin polymeric layer. Then, the cell compatibility was evaluated in Caco2 cell monolayers, an in vitro model of the intestinal epithelium. Finally, the encapsulation of the hydrophobic anti-helmintic drug nitazoxanide was studied. Cargoes as high as 17.5% w/w were achieved and the sustained release of the cargo according to the Korsmeyer- Peppas model demonstrated in vitro. Overall, preliminary results highlight the potential of this novel approach to extend the applicability of PMs in drug delivery. © 2017 Elsevier Ltd. All rights reserved. 1. Introduction Poor aqueous solubility and low physicochemical stability of drugs is one of the most significant challenges in pharmaceutical research and development. For instance, more than 50% of the marketed active pharmaceutical ingredients or new chemical en- tities that under different stages of preclinical and clinical research are highly hydrophobic and classified into Class II or IV of the Biopharmaceutics Classification System [1]. Moreover, a majority of the hydrophobic drugs display self-aggregation behavior that may distort the understanding of the drug structure-biological properties relationship, which leads to ruling out of compounds with potential therapeutic benefit [2]. In this scenario, a plethora of nanotechnology platforms have been investigated over the last decades to improve the pharma- cokinetics and pharmacodynamics of active compounds [3,4]. Polymeric micelles (PMs) are colloidal systems generated upon self-assembly of amphiphilic copolymers once the critical micellar concentration (CMC) is surpassed. Owing to the great chemical flexibility to tailor molecular features, such as hydrophilic- lipophilic balance (HLB) and self-aggregation behavior, shape, size and surface charge, functionality [5e8], and the relatively straightforward production and scalability [8], they represent one of the most versatile nanotechnology platforms for parenteral and non-parenteral delivery of hydrophobic drugs [3]. Despite the enthusiasm and the very profuse research around them [3,9], their limited physical stability and disassembly under extreme dilution * Corresponding author. Department of Materials Science and Engineering, De- Jur Building, Office 607, Technion-Israel Institute of Technology, Technion City, 3200003 Haifa, Israel. E-mail addresses: alesosnik@gmail.com, sosnik@tx.technion.ac.il (A. Sosnik). Contents lists available at ScienceDirect Materials Today Chemistry journal homepage: www.journals.elsevier.com/materials-today-chemistry/ http://dx.doi.org/10.1016/j.mtchem.2016.12.001 2468-5194/© 2017 Elsevier Ltd. All rights reserved. Materials Today Chemistry 3 (2017) 15e26