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环糊精聚合物功能化羟基磷灰石涂层钛髋关节假体对抗生素的吸附能力及抗菌性能评估

Evaluation of sorption capacity of antibiotics and antibacterial properties of a cyclodextrin-polymer functionalized hydroxyapatite-coated titanium hip prosthesis.

作者信息

Taha Mariam, Chai Feng, Blanchemain Nicolas, Neut Christel, Goube Michel, Maton Mickael, Martel Bernard, Hildebrand Hartmut F

机构信息

Université Lille Nord De France, 59000 Lille, France; INSERM U1008, Controlled Drug Delivery System and Biomaterials, University Lille 2, F-59006 Lille, France.

Université Lille Nord De France, 59000 Lille, France; INSERM U1008, Controlled Drug Delivery System and Biomaterials, University Lille 2, F-59006 Lille, France.

出版信息

Int J Pharm. 2014 Dec 30;477(1-2):380-9. doi: 10.1016/j.ijpharm.2014.10.026. Epub 2014 Oct 17.

Abstract

Infection still present as one of common complications after total hip replacement (∼2.5%), which may cause serious outcomes. For preventing such risk, loading antibiotics onto implants for increasing local drug concentration at targeted sites could be a solution. This study aims at modifying the surface of hydroxyapatite (HA) coated titanium hip implant material (Ti-HA) with polymer of cyclodextrin (polyCD) for loading antibiotics, to achieve a sustained local drug delivery. Two widely applied antibiotics (tobramycin and rifampicin) in orthopedic surgery were loaded alone or in combination. The drug adsorption isotherm, drug release kinetics and drug's efficacy were thoroughly investigated. The results proved that polyCD coating significantly improved the affinity of both drugs to Ti-HA surface, while the mechanism of drug-polyCD interaction varies from the nature of drug, courtesy of the structural complex of polyCD. The advantage of dual-drug loading was highlighted by its strong efficacy against both Staphylococcus aureus and Enterobacter cloacae, which overcomes the limitation of mono-drug loading for an effective treatment against both bacterial strains. The prolonged antibacterial activity of antibiotic loaded Ti-HA-polyCD samples confirmed that polyCD could be a promising drug-delivery system, for sustained antibiotics release or other potential applications e.g., antimitotic agent release.

摘要

感染仍是全髋关节置换术后常见并发症之一(约2.5%),可能导致严重后果。为预防此类风险,将抗生素负载于植入物上以提高靶向部位的局部药物浓度可能是一种解决方案。本研究旨在用环糊精聚合物(聚环糊精)修饰羟基磷灰石(HA)涂层钛髋关节植入材料(Ti-HA)的表面以负载抗生素,从而实现局部药物的持续递送。单独或联合负载了骨科手术中两种广泛应用的抗生素(妥布霉素和利福平)。对药物吸附等温线、药物释放动力学及药物疗效进行了深入研究。结果证明,聚环糊精涂层显著提高了两种药物对Ti-HA表面的亲和力,而药物与聚环糊精的相互作用机制因药物性质而异,这得益于聚环糊精的结构复合物。双药负载的优势体现在其对金黄色葡萄球菌和阴沟肠杆菌均具有强大的疗效,克服了单药负载在有效治疗这两种菌株方面的局限性。负载抗生素的Ti-HA-聚环糊精样品的抗菌活性延长证实,聚环糊精可能是一种有前景的药物递送系统,用于抗生素的持续释放或其他潜在应用,如抗有丝分裂剂的释放。

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