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载双氯芬酸钠可生物降解植入式基质治疗骨髓炎:控释与骨整合。

Dual effect biodegradable ciprofloxacin loaded implantable matrices for osteomyelitis: controlled release and osteointegration.

机构信息

a Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy , Taibah University, Al-Madinah Al-Munawwarah , Saudi Arabia.

b Research and Development Department , European Egyptian Pharmaceutical Industries , Alexandria , Egypt.

出版信息

Drug Dev Ind Pharm. 2018 Jun;44(6):1023-1033. doi: 10.1080/03639045.2018.1430820. Epub 2018 Mar 14.

DOI:10.1080/03639045.2018.1430820
PMID:29484904
Abstract

Ciprofloxacin biodegradable implantable matrices (CPX-IMs) of tailored porous surfaces were fabricated by hot melt injection molding of poly-l-lactic acid (PLLA) followed by coating with PLLA/sodium chloride. CPX-IDs were designed to have a non-porous coat (NPC) or a porous coat of small pore size (SPC; 150-250 µm) or a large pore size (LPC; 250-350 µm). CPX-IMs surface pore size was confirmed by scanning electron microscope. The hardness of NPC, LPC, and SPC CPX-IMs were 58 ± 2.8, 53 ± 1.9, and 50 ± 2.1 N, respectively. The measured porosity values were 41.2 ± 1.53, 65.2 ± 1.1, and 60.7 ± 1.2%, respectively. Differential scanning calorimetry was employed to study the compatibility of ingredients, the effect of injection molding on polymer properties, and implants degradation. Coating of CPX-IMs prolonged drug release to reach a value of 90% release in 40 days. Antibacterial activity tests showed sufficiency of CPX to inhibit pathogens known to cause osteomyelitis. The in vivo study showed tissue compatibilities of the inserted matrices in tested rats with no sign of infection throughout the experiment period. SPC and LPC CPX-IMs demonstrated a better osteointegration, cell adhesion, and infiltration of different types of bone cells within implants structure compared to the non-porous matrix. Furthermore, LPC CPX-IMs showed a superior bone cell attachment and osteointegration relative to SPC CPX-IMs. Findings of this study confirmed the impact of porosity and pore sizes on cell proliferation and fracture healing concurrently with the sustained local antibiotic therapy for treatment or prevention of osteomyelitis.

摘要

定制多孔表面的环丙沙星可生物降解植入式基质 (CPX-IM) 是通过聚 L-乳酸 (PLLA) 的热熔注塑成型,然后用 PLLA/氯化钠进行涂层制成的。CPX-ID 设计为具有无孔涂层 (NPC) 或小孔尺寸的多孔涂层 (SPC;150-250 µm) 或大孔尺寸的多孔涂层 (LPC;250-350 µm)。CPX-IM 表面孔径通过扫描电子显微镜确认。NPC、LPC 和 SPC CPX-IM 的硬度分别为 58 ± 2.8、53 ± 1.9 和 50 ± 2.1 N。测量的孔隙率值分别为 41.2 ± 1.53%、65.2 ± 1.1%和 60.7 ± 1.2%。差示扫描量热法用于研究成分的相容性、注塑对聚合物性能的影响和植入物的降解。CPX-IM 的涂层延长了药物释放,达到 40 天释放 90%的药物释放值。抗菌活性测试表明 CPX 足以抑制已知引起骨髓炎的病原体。体内研究表明,在所测试的大鼠中,插入的基质具有组织相容性,整个实验期间没有感染的迹象。与非多孔基质相比,SPC 和 LPC CPX-IM 显示出更好的骨整合、细胞黏附以及不同类型的骨细胞在植入物结构内的渗透。此外,LPC CPX-IM 显示出比 SPC CPX-IM 更好的骨细胞附着和骨整合。这项研究的结果证实了孔隙率和孔径对细胞增殖和骨折愈合的影响,同时进行局部抗生素治疗以治疗或预防骨髓炎。

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