title: Processing and sustained in vitro release of rifampicin containing composites to enhance the treatment of osteomyelitis.
abstract: The objective in this study was to develop an osteoconductive, biodegradable and rifampicin releasing bone filling composite material for the treatment of osteomyelitis, a bacterial infection of bone that is very difficult and expensive to treat. The composite material will be used together with a ciprofloxacin releasing composite, because of the rapid development of resistant bacteria when rifampicin is used alone. Three composites were manufactured by twin-screw extrusion. The polymer matrix for the composites was poly(L-lactide-co-ε-caprolactone) 70/30 and all the composites contained 8 wt% (weight percent) of rifampicin antibiotic. The β-TCP contents of the composites were 0 wt%, 50 wt% and 60 wt%. The composites were sterilized by gamma irradiation before in vitro degradation and drug release tests. The hydrolytical degradation of the studied composites proceeded quickly and the molecular weight of the polymer component of the composites decreased rapidly. Rifampicin release occurred in four phases in which the high β-TCP content of the samples, polymer degradation and mass loss all played a role in determining the phases. The ceramic component was seen to have a positive effect on the drug release. The composite with 50 wt% of β-TCP showed the most promising rifampicin release profile and it also showed activity against a common osteomyelitis causing bacteria Pseudomonas aeruginosa. A clear inhibition zone was formed in 16 h incubation. Overall, the tested materials showed great potential to be developed into a bone filler material for the treatment of osteomyelitis or other bone related infections in combination with the ciprofloxacin releasing materials.
authors.affiliation: Department of Biomedical Engineering, Tampere University of Technology, Tampere, Finland. niina.ahola@tut.fi
authors.forename: Niina
authors.initials: N
authors.lastname: Ahola
authors.forename: Minna
authors.initials: M
authors.lastname: Veiranto
authors.forename: Noora
authors.initials: N
authors.lastname: Männistö
authors.forename: Matti
authors.initials: M
authors.lastname: Karp
authors.forename: Jaana
authors.initials: J
authors.lastname: Rich
authors.forename: Alexander
authors.initials: A
authors.lastname: Efimov
authors.forename: Jukka
authors.initials: J
authors.lastname: Seppälä
authors.forename: Minna
authors.initials: M
authors.lastname: Kellomäki
mesh_terms: D000042:Absorption; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry; D018786:Bone Substitutes / Q000737:chemistry*; D001842:Bone and Bones / Q000187:drug effects; D002130:Calcium Phosphates / Q000737:chemistry*; D002516:Ceramics / Q000737:chemistry; D002939:Ciprofloxacin / Q000737:chemistry; D016503:Drug Delivery Systems; D024881:Drug Resistance, Bacterial; D006868:Hydrolysis; D008422:Materials Testing; D008970:Molecular Weight; D010019:Osteomyelitis / Q000188:drug therapy*; D011091:Polyesters / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012293:Rifampin / Q000008:administration & dosage*; D013696:Temperature; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D011091:Polyesters; C485817:beta-tricalcium phosphate; D002939:Ciprofloxacin; C062968:lactide-caprolactone copolymer; D012293:Rifampin
keywords: antibiotic; biodegradable; drug release; poly(L-lactide-co-caprolactone); polylactide; rifampicin