Tuning the size and hydrophobicity of nanohydrogels exploiting a self-assembly assisted polymerization mechanism for con
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RESEARCH PAPER
Tuning the size and hydrophobicity of nanohydrogels exploiting a self-assembly assisted polymerization mechanism for controlled drug delivery Sarin Palakkal & Dana Logviniuk & Gerardo Byk
Received: 15 January 2020 / Accepted: 17 November 2020 # Springer Nature B.V. 2020
Abstract We have designed series of monodispersed nanohydrogels (NHGs) with sizes ranging from 20 to 400 nm, generated from mixtures of Nisopropylacrylamide, di-block (hydrophilic-hydrophobic), and tri-block (hydrophobic-hydrophilic-hydrophobic) copolymer acrylamide macro-monomers. When the monomers are mixed at high temperature they collapse into well-defined self-assemblies, which can be further polymerized leading to cross-linked NHGs with sizes matching the intermediate self-assemblies. The size of the self-assemblies can be tuned/calibrated by combining different ratios of the starting monomeric mixtures at high temperature. Herein, we defined the concept of” phantom monomers” which are the closest structure that mimic a selected monomer but lacks the active function for polymerization. The phantom monomer co-formulated with other monomers will be present in the intermediate selfassemblies due to its similarity with one of the active monomers. However, upon polymerization, the phantom monomer, lacking of a polymerizable function, will be excluded and a new NHGs will be generated. The comparative analyses of our previously obtained standard NHGs (G1) with those obtained here using phantom monomers (G2 and G3) not only put in evidence the S. Palakkal : G. Byk (*) Department of Chemistry, Laboratory of Nano-Biotechnology, Bar Ilan University, 52900 Ramat Gan, Israel e-mail: [email protected] D. Logviniuk School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, TelAviv University, 6997801 Tel Aviv, Israel
self-assembly mediated mechanism but also prove the generation of new monodispersed NHG’s with improved drug-loading properties. As proof of concept, the NHGs were loaded with doxorubicin (DOX) and tested in cells. Results indicate that the drug-loading of the NHGs increases from G1 to G3 and while using the same drug concentration, different size NHGs affect differently the treated cells and disclose a different activity and localization as compared to free DOX by confocal microscopy. Keywords Self-assembly . Polymerization . Thermo-responsivity . Controlled drug release . Intracellular tracking . Doxorubicin . Forster resonance energy transfer . Nanostructures
Introduction Nanohydrogels (NHGs) are remarkably useful for drug delivery because they can reach the smallest capillary vessels, not accessible to macroscale hydrogels, and penetrate tissues either through the paracellular or transcellular pathways. The size and surface properties of NHGs can be tailored to avoid a rapid clearance by phagocytic cells, with a concomitant increment of circulation times that allows improved passive and active drug targeting. Hydrogel-based delivery systems are being used for oral, rectal, ocular, epidermal, and subcu
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