Liposomal hydrogel surface coatings for localized delivery of therapeutic compounds

grantor: University of TorontoA novel coating combining the delayed release properties of antibiotic-loaded liposomes with the structural advantages of crosslinked gelatin gels was developed in an effort to reduce bacterial adhesion to silicone catheters. The covalent bonding of liposomal gels to silicone surfaces was accomplished by modification of silicone surface chemistry. Application of gelatin substituted with 4-azido-2,3,5,6-tetrafluorobenzoic acid (AFB-gelatin) to a silicone surface followed by exposure to ultraviolet radiation led to the formation of surface-bound crosslinked gelatin. Alternatively, reactive groups were introduced onto silicone surfaces through a photochemical graft polymerization process. The bonding strength of gel coatings to either AFB-gelatin-modified silicone or poly (acrylic acid)-grafted silicone was found to increase approximately thirty-fold or fifty-fold, respectively, relative to unmodified silicone. Liposomes sequestered within crosslinked gelatin gels compromised neither the thermal stability nor the mechanical strength of the hydrogel matrix. The liposome bilayer was minimally affected by interaction with gelatin. The level of liposome release from gels was influenced by liposome concentration and size, as well as the presence of poly (ethylene oxide) [PEO]; PEO chains in the gel matrix or liposome membrane tended to promote release. The ' in vitro' efflux rates of ciprofloxacin and chlorhexidine from liposomal gels were affected by the type of medium in which the gels were immersed, with the highest release rate observed for ciprofloxacin-loaded gels in 50% serum. 'In vitro' and 'in vivo' assays using a clinical isolate of 'Pseudomonas aeruginosa' established the antimicrobial efficacy of ciprofloxacin-loaded liposomal hydrogels. Agar diffusion assays produced substantial growth inhibition zones for as long as 16 d, while bacterial colonization was completely inhibited on coated catheter surfaces throughout a seven-day 'in vitro' static adhesion assay. ' P. aeruginosa' adhesion under continuous flow conditions also was reduced on liposomal hydrogels relative to controls. An animal model of urinary tract infection using rabbits catheterized for an average of six days revealed the absence of viable 'Escherichia coli' on coated catheters in 7 out of 9 cases, while all untreated catheter surfaces examined (n = 7) were contaminated. This new antimicrobial coating has potential as a prophylactic for catheter-related nosocomial urinary tract infection.Ph.D