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新型载万古霉素骨样羟基磷灰石/聚氨基酸支架的体外和体内药物释放及抗菌性能

In vitro and in vivo drug release and antibacterial properties of the novel vancomycin-loaded bone-like hydroxyapatite/poly amino acid scaffold.

作者信息

Cao Zhidong, Jiang Dianming, Yan Ling, Wu Jun

机构信息

Department of Orthopedics, The Emergency Medical Center of Chongqing City, Chongqing, People's Republic of China.

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

出版信息

Int J Nanomedicine. 2017 Mar 8;12:1841-1851. doi: 10.2147/IJN.S122864. eCollection 2017.

Abstract

Antibiotic-loaded carriers were developed to fill cavities and locally deliver antibiotics following implantation. However, the most commonly used antibiotic carrier, polymethyl methacrylate (PMMA), has many disadvantages including that it does not promote bone regeneration or conduction. Vancomycin-loaded bone-like hydroxyapatite/poly amino acid (V-BHA/PAA) was successfully fabricated by a homogeneous method, certified as biosafe and known to promote osteogenesis. To evaluate its drug-release features, the quantity of the vancomycin in the elution was obtained every 2 days after in vitro simulated body fluid immersion. The drug concentration in the elution was determined to obtain the drug-release curve. The in vitro drug release was a three-phase process with two release peaks. Its antibacterial activity was evaluated in vitro using an antibacterial zone assay, antibacterial inhibition, and scanning electron microscopy (SEM) observation. Scaffolds of V-BHA/PAA were implanted into a rabbit model of chronic osteomyelitis. The antibacterial activity of the material was evaluated in vivo by gross observations, X-ray, and histological and ultrastructural observations. During the first 48 h, the vancomycin release was more rapid, followed by a period of sustained slow release. Use of V-BHA/PAA could achieve relatively long-term vancomycin delivery of 38 days in vitro and 42 days in vivo. V-BHA/PAA showed a significant and consistent bactericidal effect toward both and methicillin-resistant (MRSA) in vitro and in vivo. Moreover, the bactericidal effect was stronger than that of vancomycin-loaded polymethyl meth acrylate (V-PMMA). The duration of the antibacterial effect of V-BHA/PAA toward both and MRSA exceeded 28 days in vitro, while that of V-PMMA lasted only 14 days. The curative rate for V-BHA/PAA in the chronic osteomyelitis model was 75% for regular and 66.67% for MRSA infection, which significantly exceeded that of V-PMMA (50% and 41.67%, respectively). Vancomycin released from the V-BHA/PAA scaffold was significantly superior to that delivered by V-PMMA.

摘要

载抗生素载体被研发用于填充骨腔,并在植入后局部递送抗生素。然而,最常用的抗生素载体聚甲基丙烯酸甲酯(PMMA)有许多缺点,包括它不能促进骨再生或骨传导。通过均相法成功制备了载万古霉素的类骨羟基磷灰石/聚氨基酸(V-BHA/PAA),经认证具有生物安全性且已知能促进成骨。为评估其药物释放特性,在体外模拟体液浸泡后每2天测定洗脱液中万古霉素的量。测定洗脱液中的药物浓度以获得药物释放曲线。体外药物释放是一个具有两个释放峰的三相过程。使用抑菌圈试验、抗菌抑制和扫描电子显微镜(SEM)观察在体外评估其抗菌活性。将V-BHA/PAA支架植入慢性骨髓炎兔模型中。通过大体观察、X射线以及组织学和超微结构观察在体内评估该材料的抗菌活性。在最初的48小时内,万古霉素释放较快,随后是一段持续缓慢释放的时期。使用V-BHA/PAA在体外可实现38天、在体内可实现42天的相对长期万古霉素递送。V-BHA/PAA在体外和体内对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌(MRSA)均显示出显著且持续的杀菌作用。此外,杀菌作用比载万古霉素的聚甲基丙烯酸甲酯(V-PMMA)更强。V-BHA/PAA对金黄色葡萄球菌和MRSA的抗菌作用持续时间在体外超过28天,而V-PMMA仅持续14天。在慢性骨髓炎模型中,V-BHA/PAA对普通金黄色葡萄球菌的治愈率为75%,对MRSA感染的治愈率为66.67%,显著超过V-PMMA(分别为50%和41.67%)。从V-BHA/PAA支架释放的万古霉素明显优于V-PMMA递送的万古霉素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a05b/5352232/83782193714d/ijn-12-1841Fig1.jpg

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