title: Novel semi-interpenetrating hydrogel networks with enhanced mechanical properties and thermoresponsive engineered drug delivery, designed as bioactive endotracheal tube biomaterials.
abstract: Thermoresponsive polymeric platforms are used to optimise drug delivery in pharmaceutical systems and bioactive medical devices. However, the practical application of these systems is compromised by their poor mechanical properties. This study describes the design of thermoresponsive semi-interpenetrating polymer networks (s-IPNs) based on cross-linked p(NIPAA) or p(NIPAA-co-HEMA) hydrogels containing poly(ε-caprolactone) designed to address this issue. Using DSC, the lower critical solution temperature of the co-polymer and p(NIPAA) matrices were circa 34°C and 32°C, respectively. PCL was physically dispersed within the hydrogel matrices as confirmed using confocal scanning laser microscopy and DSC and resulted in marked changes in the mechanical properties (ultimate tensile strength, Young's modulus) without adversely compromising the elongation properties. P(NIPAA) networks containing dispersed PCL exhibited thermoresponsive swelling properties following immersion in buffer (pH 7), with the equilibrium-swelling ratio being greater at 20°C than 37°C and greatest for p(NIPAA)/PCL systems at 20°C. The incorporation of PCL significantly lowered the equilibrium swelling ratio of the various networks but this was not deemed practically significant for s-IPNs based on p(NIPAA). Thermoresponsive release of metronidazole was observed from s-IPN composed of p(NIPAA)/PCL at 37°C but not from p(NIPAA-co-HEMA)/PCL at this temperature. In all other platforms, drug release at 20°C was significantly similar to that at 37°C and was diffusion controlled. This study has uniquely described a strategy by which thermoresponsive drug release may be performed from polymeric platforms with highly elastic properties. It is proposed that these materials may be used clinically as bioactive endotracheal tubes, designed to offer enhanced resistance to ventilator associated pneumonia, a clinical condition associated with the use of endotracheal tubes where stimulus responsive drug release from biomaterials of significant mechanical properties would be advantageous.
authors.affiliation: School of Pharmacy, Queen's University of Belfast, Northern Ireland, United Kingdom. d.jones@qub.ac.uk
authors.forename: David S
authors.initials: DS
authors.lastname: Jones
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Andrews
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Caldwell
authors.forename: Colin
authors.initials: C
authors.lastname: Lorimer
authors.forename: Sean P
authors.initials: SP
authors.lastname: Gorman
authors.forename: Colin P
authors.initials: CP
authors.lastname: McCoy
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003432:Cross-Linking Reagents / Q000737:chemistry; D004058:Diffusion; D016503:Drug Delivery Systems; D004548:Elasticity; D004867:Equipment Design; D020100:Hydrogels; D007442:Intubation, Intratracheal / Q000295:instrumentation*; D008689:Methacrylates / Q000737:chemistry; D008795:Metronidazole / Q000008:administration & dosage*; D018613:Microscopy, Confocal; D011091:Polyesters / Q000737:chemistry; D013696:Temperature; D013718:Tensile Strength
chemical_list: D000178:Acrylamides; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D008689:Methacrylates; D011091:Polyesters; D008795:Metronidazole; C016240:polycaprolactone; C005044:hydroxyethyl methacrylate; C067295:N-isopropylacrylamide