title: Transiently Responsive Block Copolymer Micelles Based on N-(2-Hydroxypropyl)methacrylamide Engineered with Hydrolyzable Ethylcarbonate Side Chains.
abstract: The lack of selectivity and low solubility of many chemotherapeutics impels the development of different biocompatible nanosized drug carriers. Amphiphilic block copolymers, composed of a hydrophilic and hydrophobic domain, show great potential because of their small size, large solubilizing power and loading capacity. In this paper, we introduce a new class of degradable temperature-responsive block copolymers based on the modification of N-(2-hydroxypropyl)methacrylamide (HPMA) with an ethyl group via a hydrolytically sensitive carbonate ester, polymerized by radical polymerization using a PEG-based macroinitiatior. The micellization and temperature-responsive behavior of the PEG-poly(HPMA-EC) block copolymer were investigated by dynamic light scattering (DLS). We observed that the polymer exhibits lower critical solution temperature (LCST) behavior and that above the cloud point (cp) of 17 °C the block copolymer self-assembles in micelles with a diameter of 40 nm. Flow cytometry analysis and confocal microscopy show a dose-dependent cellular uptake of the micelles loaded with a hydrophobic dye. The block copolymer nanoparticles were capable of delivering the hydrophobic payload into cancer cells in both 2D and 3D in vitro cultures. The block copolymer has excellent cytocompatibility, whereas loading the particles with the hydrophobic anticancer drug paclitaxel results in a dose-dependent decrease in cell viability.
authors.affiliation: Department of Pharmaceutics, Ghent University , 9000 Ghent, Belgium.
authors.forename: Sabah
authors.initials: S
authors.lastname: Kasmi
authors.affiliation: Department of Pharmaceutics, Ghent University , 9000 Ghent, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Louage
authors.affiliation: Department of Pharmaceutics, Ghent University , 9000 Ghent, Belgium.
authors.forename: Lutz
authors.initials: L
authors.lastname: Nuhn
authors.affiliation: Department of Pharmaceutics, Ghent University , 9000 Ghent, Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Van Driessche
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital , 9000 Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van Deun
authors.affiliation: Department of Pharmaceutics, Ghent University , 9000 Ghent, Belgium.
authors.forename: Izet
authors.initials: I
authors.lastname: Karalic
authors.affiliation: Department of Pharmaceutics, Ghent University , 9000 Ghent, Belgium.
authors.forename: Martijn
authors.initials: M
authors.lastname: Risseeuw
authors.affiliation: Department of Pharmaceutics, Ghent University , 9000 Ghent, Belgium.
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
authors.affiliation: Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University , 9000 Ghent, Belgium.
authors.forename: Richard
authors.initials: R
authors.lastname: Hoogenboom
authors.affiliation: VIB inflammation Research Center , Zwijnaarde, 9052 Ghent, Belgium.
authors.forename: Riet
authors.initials: R
authors.lastname: De Rycke
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital , 9000 Ghent, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , 3512 JE Utrecht, The Netherlands.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.affiliation: Department of Pharmaceutics, Ghent University , 9000 Ghent, Belgium.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: De Geest
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013696:Temperature
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011092:Polyethylene Glycols; D017239:Paclitaxel; C032976:N-(2-hydroxypropyl)methacrylamide