Characterization of the physicochemical, antimicrobial, and drug release properties of thermoresponsive hydrogel copolymers designed for medical device applications.
In this study, a series of hydrogels was synthesized by free radical polymerization, namely poly(2-(hydroxyethyl)methacrylate) (pHEMA), poly(4-(hydroxybutyl)methacrylate) (pHBMA), poly(6-(hydroxyhexyl)methacrylate) (pHHMA), and copolymers composed of N-isopropylacrylamide (NIPAA), methacrylic acid (MA), NIPAA, and the above monomers. The surface, mechanical, and swelling properties (at 20 and 37 degrees C, pH 6) of the polymers were determined using dynamic contact angle analysis, tensile analysis, and thermogravimetry, respectively. The T(g) and lower critical solution temperatures (LCST) were determined using modulated DSC and oscillatory rheometry, respectively. Drug loading of the hydrogels with chlorhexidine diacetate was performed by immersion in a drug solution at 20 degrees C (<LCST) and subsequent characterization of the drug release and antimicrobial properties performed at 20 and 37 degrees C. The composition of the hydrogels directly affected the advancing contact angle, mechanical properties, and swelling. Thermoresponsive behavior was only observed with hydrogels composed of HEMA, NIPAA, MA, and NIPAA in which pulsatile drug release was obtained by elevating the temperature from below to above the LCST. A greater mass and enhanced pulsatile release of drug, with the associated greater antimicrobial properties (an 10(8) reduction in viability of Staphylococcus epidermidis in 15 min), was associated with poly(NIPAA-co-HEMA, 1:1). It is suggested that the pulsatile drug release and favorable antimicrobial and mechanical properties of candidate hydrogels, particularly poly(HEMA-co-NIPAA), offer promise as thermoresponsive, antimicrobial biomaterials that may be used as wound dressings, medical implants, or coatings of medical devices. Furthermore, it is suggested that drug loading may be effectively performed in situ by lowering the temperature of the device/dressing.
Jones
David S
DS
Medical Devices Group, School of Pharmacy, The Queen's University of Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. d.jones@qub.ac.uk
Lorimer
Colin P
CP
McCoy
Colin P
CP
Gorman
Sean P
SP
D000891:Anti-Infective Agents, Local / Q000737:chemistry* / Q000494:pharmacology; D002710:Chlorhexidine / Q000737:chemistry* / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry; D006358:Hot Temperature; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry*; D008422:Materials Testing / Q000379:methods; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D013291:Streptococcus / Q000254:growth & development*; D013499:Surface Properties; D013997:Time Factors
D000891:Anti-Infective Agents, Local; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D020100:Hydrogels; D011109:Polymethacrylic Acids; D002710:Chlorhexidine