title: Photopolymerized thermosensitive hydrogels for tailorable diffusion-controlled protein delivery.
abstract: In this paper the possibility to tailor degradation and protein release behavior of photopolymerized thermosensitive hydrogels is studied. The hydrogels consist of ABA triblock copolymer, in which the thermosensitive A-blocks are methacrylated poly(N-(2-hydroxypropyl)methacrylamide lactate)s and the B-block is poly(ethylene glycol) with molecular weight of 10 kDa. These hydrogels are prepared by using a combination of physical and chemical cross-linking methods. When a solution of a thermosensitive methacrylated p(HPMAm-lac)-PEG-p(HPMAm-lac) is heated above its cloud point a viscoelastic material is obtained, which can be stabilized by introducing covalent cross-links by photopolymerization. By varying the polymer concentration, hydrogels with different mechanical properties are formed, of which the cross-linking density, mesh size, swelling and degradation behavior can be tuned. It was demonstrated that the release rate of three model proteins (lysozyme, BSA and IgG, with hydrodynamic diameters ranging from 4.1 to 10.7 nm) depended on the protein size and hydrogel molecular weight between cross-links and was governed by the Fickian diffusion. Importantly, the encapsulated proteins were quantitatively released and the secondary structure and the enzymatic activity of lysozyme were fully preserved demonstrating the protein friendly nature of the studied delivery system.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, Sorbonnelaan 16, 3508 TB Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Censi
authors.forename: T
authors.initials: T
authors.lastname: Vermonden
authors.forename: M J
authors.initials: MJ
authors.lastname: van Steenbergen
authors.forename: H
authors.initials: H
authors.lastname: Deschout
authors.forename: K
authors.initials: K
authors.lastname: Braeckmans
authors.forename: S C
authors.initials: SC
authors.lastname: De Smedt
authors.forename: C F
authors.initials: CF
authors.lastname: van Nostrum
authors.forename: P
authors.initials: P
authors.lastname: di Martino
authors.forename: W E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D000178:Acrylamides; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D016503:Drug Delivery Systems; D036681:Fluorescence Recovery After Photobleaching; D020100:Hydrogels / Q000737:chemistry*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000737:chemistry; D007773:Lactates; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates / Q000737:chemistry; D008970:Molecular Weight; D009113:Muramidase / Q000008:administration & dosage / Q000493:pharmacokinetics; D011092:Polyethylene Glycols; D011506:Proteins / Q000008:administration & dosage*; D012212:Rheology; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: D000178:Acrylamides; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D007074:Immunoglobulin G; D007773:Lactates; D008689:Methacrylates; D011506:Proteins; C509680:poly(N-(2-hydroxypropyl) methacrylamide lactate); D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D009113:Muramidase