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载庆大霉素多糖膜在防治骨骼系统术后感染中的应用

Gentamicin-Loaded Polysaccharide Membranes for Prevention and Treatment of Post-operative Wound Infections in the Skeletal System.

机构信息

Department of Biomaterials, AGH University of Science and Technology, Faculty of Materials Science and Ceramics, al. A. Mickiewicza 30, 30-059, Kraków, Poland.

Department of Microbiology, Jagiellonian University, Medical College, ul. Czysta 18, 31-121, Kraków, Poland.

出版信息

Pharm Res. 2017 Oct;34(10):2075-2083. doi: 10.1007/s11095-017-2212-5. Epub 2017 Jun 21.

Abstract

PURPOSE

To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections.

METHODS

Membranes made of gellan gum (GUM), sodium alginate (ALG), GUM and ALG crosslinked with calcium ions (GUM + Ca and ALG + Ca, respectively) as well as reference collagen (COL) were produced by freeze-drying. Mechanical properties, drug release, antimicrobial activity and cytocompatibility of the membranes were assessed.

RESULTS

The most appropriate handling and mechanical properties (Young's modulus, E = 92 ± 4 MPa and breaking force, F  = 2.6 ± 0.1 N) had GUM + Ca membrane. In contrast, COL membrane showed F  = 0.14 ± 0.02 N, E = 1.0 ± 0.3 MPa and was deemed to be unsuitable for antibiotic delivery. The pharmacokinetic data demonstrated a uniform and sustainable delivery of gentamicin from GUM + Ca (44.4 ± 1.3% within 3 weeks), while for COL, ALG and ALG + Ca membranes the most of the drug was released within 24 h (55.3 ± 1.9%, 52.5 ± 1.5% and 37.5 ± 1.8%, respectively). Antimicrobial activity against S. aureus and S. epidermidis was confirmed for all the membranes. GUM + Ca and COL membranes supported osteoblasts growth, whereas on ALG and ALG + Ca membranes cell growth was reduced.

CONCLUSIONS

GUM + Ca membrane holds promise for effective treatment of bone infections thanks to favorable pharmacokinetics, bactericidal activity, cytocompatibility and good mechanical properties.

摘要

目的

开发基于多糖的膜,使庆大霉素能够得到控制和局部递送,用于治疗术后骨感染。

方法

通过冷冻干燥制备了葡聚糖胶(GUM)、海藻酸钠(ALG)、GUM 和 ALG 分别与钙离子交联的膜(GUM+Ca 和 ALG+Ca)以及参考胶原(COL)膜。评估了膜的机械性能、药物释放、抗菌活性和细胞相容性。

结果

GUM+Ca 膜具有最合适的处理和机械性能(杨氏模量,E=92±4MPa 和断裂力,F=2.6±0.1N)。相比之下,COL 膜的 F=0.14±0.02N,E=1.0±0.3MPa,被认为不适合抗生素输送。药代动力学数据表明,庆大霉素从 GUM+Ca 中均匀且持续释放(3 周内为 44.4±1.3%),而 COL、ALG 和 ALG+Ca 膜中的大部分药物在 24 小时内释放(分别为 55.3±1.9%、52.5±1.5%和 37.5±1.8%)。所有膜均证实对金黄色葡萄球菌和表皮葡萄球菌具有抗菌活性。GUM+Ca 和 COL 膜支持成骨细胞的生长,而 ALG 和 ALG+Ca 膜上的细胞生长减少。

结论

由于良好的药代动力学、杀菌活性、细胞相容性和良好的机械性能,GUM+Ca 膜有望成为治疗骨感染的有效方法。

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