title: Pseudopolyrotaxane Formation in the Synthesis of Cyclodextrin Polymers: Effects on Drug Delivery, Mechanics, and Cell Compatibility.
abstract: Numerous groups have reported the use of cyclodextrin (CD)-based polymers for drug delivery applications due to their capacity to form inclusions with small molecule drugs, delaying the rate of drug release beyond that of diffusion alone (termed "affinity-based" drug delivery). Herein we demonstrate synthesis and characterization of a new family of CD-based polymers, some as pseudopolyrotaxanes, generated under mild (aqueous, room temperature) conditions. The formation of these new affinity polymers results in broad mechanical properties. Three diglycidylether cross-linkers which vary in length from 0 to 10 ethylene glycol units were examined. Pseudopolyrotaxane formation was found only with the highest-length cross-linker, noted first by a sharp change in both material properties and then confirmed by chemical signature. Materials were thoroughly evaluated by NMR, DSC, DMA, TGA, XRD, and FTIR. Cross-linker choice was also tested for impact on drug loading and delivery capacity, using antibiotics as model drugs. Chemically similar polymers without showing affinity rapidly saturated in loading experiments, while affinity materials showing high capacity for drug loading, even beyond the solubility limit of the drugs. When using the polymers with these new cross-linkers, affinity-based drug delivery is maintained: the materials are capable of antibiotic delivery, and clearance of Staphylococcus aureus, at least an order of magnitude better than diffusion-only control polymers. In cell compatibility studies, CD-based polymers were shown to have low overt cell toxicity and even resisted cell adhesion, presumably due to their highly hydrated state.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Thimma R
authors.initials: TR
authors.lastname: Thatiparti
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Dajan
authors.initials: D
authors.lastname: Juric
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Horst A
authors.identifier: 0000-0002-9323-8100
authors.initials: HA
authors.lastname: von Recum
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000138:chemical synthesis*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003505:Cyclodextrins / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D051379:Mice; D041681:NIH 3T3 Cells; D020442:Poloxamer / Q000737:chemistry*; D043862:Rotaxanes / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D003505:Cyclodextrins; D043862:Rotaxanes; C041953:cyclodextrin polymer; C475674:pseudopolyrotaxane; D020442:Poloxamer; D002482:Cellulose