title: Injectable hybrid delivery system composed of gellan gum, nanoparticles and gentamicin for the localized treatment of bone infections.
abstract: OBJECTIVE
  Bone infections are treated with antibiotics administered intravenously, antibiotic-releasing bone cements or collagen sponges placed directly in the infected area. These approaches render limited effectiveness due to the lack of site specificity and invasiveness of implanting cements and sponges. To address these limitations, we developed a novel polysaccharide hydrogel-based injectable system that enables controlled delivery of gentamicin (GENT). Its advantages are minimal invasiveness, and localized and finely regulated release of the drug.
  
  
  METHODS
  GENT was incorporated both directly within the gellan gum hydrogel and into poly(L-lactide-co-glycolide) nanoparticles embedded into the hydrogel.
  
  
  RESULTS
  We confirmed the injectability of the system and measured extrusion force was 15.6 ± 1.0 N, which is suitable for injections. The system set properly after the injection as shown by rheological measurements. Desired burst release of the drug was observed within the first 12 h and the dose reached ~27% of total GENT. Subsequently, GENT was released gradually and sustainably: ~60% of initial dose within 90 days. In vitro studies confirmed antimicrobial activity of the system against Staphylococcus spp. and cytocompatibility with osteoblast-like cells.
  
  
  CONCLUSIONS
  Developed injectable system enables minimally invasive, local and sustained delivery of the pharmaceutically relevant doses of GENT to combat bone infections.
authors.affiliation: a Department of Biomaterials, Faculty of Materials Science and Ceramics , AGH University of Science and Technology , Krakow , Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Posadowska
authors.affiliation: b Department of Microbiology, Medical College , Jagiellonian University , Krakow , Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Brzychczy-Włoch
authors.affiliation: a Department of Biomaterials, Faculty of Materials Science and Ceramics , AGH University of Science and Technology , Krakow , Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Drożdż
authors.affiliation: a Department of Biomaterials, Faculty of Materials Science and Ceramics , AGH University of Science and Technology , Krakow , Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krok-Borkowicz
authors.affiliation: c Laboratory of Physical Chemistry and Soft Matter , Wageningen University , Wageningen , The Netherlands.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Włodarczyk-Biegun
authors.affiliation: d Center of Polymer and Carbon Materials , Polish Academy of Sciences , Zabrze , Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dobrzyński
authors.affiliation: e Faculty of Pharmacy , The University of Sydney , Sydney , Australia.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Chrzanowski
authors.affiliation: a Department of Biomaterials, Faculty of Materials Science and Ceramics , AGH University of Science and Technology , Krakow , Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pamuła
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry*; D004337:Drug Carriers; D005839:Gentamicins / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles; D010019:Osteomyelitis / Q000188:drug therapy; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D005839:Gentamicins; D011135:Polysaccharides, Bacterial; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C048288:gellan gum
keywords: Controlled drug delivery; biocompatible materials; gellan gum; gentamicin (GENT); nanoparticles; osteomyelitis; poly(lactide-co-glycolide) (PLGA)