title: Prolonged anti-bacterial activity of ion-complexed doxycycline for the treatment of osteomyelitis.
abstract: The main purposes of the present study are the fabrication of an ion-complexed antibiotic which allows for the continuous release of the drug for sufficient periods of time without any additional matrix leading to unfavorable tissue responses, and the feasibility study of the ion-complexed antibiotic as a therapeutic system for osteomyelitis using an animal model. An ion-complexed doxycycline (icDX) as an antibiotic was prepared by simple mixing of positively charged doxycycline hyclate (DX) and negatively charged multivalent Na2HPO4 (2Na(+) HPO4(2-)) aqueous solutions. The icDX showed a controlled release of the DX up to 6 weeks. From the in vivo feasibility study using an osteomyelitis rat model, the icDX group showed a more effective therapeutic effect for the osteomyelitis, at 3 and 6 weeks, compared to the non-treated control and free DX groups. This was due to the sustained release of DX from the icDX in the osteomyelitis bone (medullary cavity) without migration. These findings suggest that the icDX may be a promising local delivery system in the clinical field for the treatment of the osteomyelitis.
authors.affiliation: Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
authors.forename: Se Heang
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Advanced Materials, Hannam University, Daejeon, Republic of Korea.
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Nam
authors.affiliation: Department of Biological Sciences and Biotechnology, Hannam University, Daejeon, Republic of Korea.
authors.forename: In Soo
authors.initials: IS
authors.lastname: Lee
authors.affiliation: Department of Advanced Materials, Hannam University, Daejeon, Republic of Korea. Electronic address: jhlee@hnu.kr.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004318:Doxycycline / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D010019:Osteomyelitis / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004318:Doxycycline
keywords: Antibiotic; Doxycycline; Drug delivery system; Ion-complexed drug; Local delivery; Osteomyelitis; Sustained release