Inflammation-Induced Drug Release by using a pH-Responsive Gas-Generating Hollow-Microsphere System for the Treatment of Osteomyelitis
Inflammation-Induced Drug Release by using a pH-Responsive Gas-Generating Hollow-Microsphere System for the Treatment of Osteomyelitis
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DOI：
10.1002/adhm.201400158
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发表时间：
2014-11-01
影响因子：
10
通讯作者：
Sung, Hsing-Wen
中科院分区：
文献类型：
--
作者：
Chung, Ming-Fan;Chia, Wei-Tso;Sung, Hsing-Wen
在骨髓炎的常规治疗中，抗生素对感染骨的渗透通常很差。为了确保局部抗生素浓度足够，本工作开发了一种可注射的磷酸钙（CP）骨水泥，其中嵌入pH响应中空微球（HMs），其可以根据局部pH控制药物的释放。（D，L -乳酸-共-乙醇酸）（PLGA）和含有万古霉素（货车）和NaHCO 3的含水核。在中性pH值下，CP/HM骨水泥洗脱的药物浓度可忽略不计。在酸性环境中，包封在HM中的NaHCO 3与酸快速反应以产生CO2气泡，破坏PLGA壳，从而局部释放超过治疗阈值的货车。采用兔骨髓炎模型研究了CP/HM骨水泥治疗骨髓炎的可行性。分析结果表明，CP/HM水泥提供了高效的局部抗菌活性。组织学检查进一步验证了CP/HM骨水泥治疗的有效性。上述结果表明，CP/HM骨水泥是治疗骨髓炎中局部递送抗生素的高效系统。
In the conventional treatment of osteomyelitis, the penetration of antibiotics into the infected bone is commonly poor. To ensure that the local antibiotic concentration is adequate, this work develops an injectable calcium phosphate (CP) cement in which is embedded pH-responsive hollow microspheres (HMs) that can control the release of a drug according to the local pH. The HMs are fabricated using a microfluidic device, with a shell of poly(D, L -lactic-co-glycolic acid) (PLGA) and an aqueous core that contains vancomycin (Van) and NaHCO3. At neutral pH, the CP/HM cement elutes a negligible concentration of the drug. In an acidic environment, the NaHCO3 that is encapsulated in the HMs reacts with the acid rapidly to generate CO2 bubbles, disrupting the PLGA shells and thereby releasing Van locally in excess of a therapeutic threshold. The feasibility of using this CP/HM cement to treat osteomyelitis is studied using a rabbit model. Analytical results reveal that the CP/HM cement provides highly effective local antibacterial activity. Histological examination further verifies the efficacy of the treatment by the CP/HM cement. The above findings suggest that the CP/HM cement is a highly efficient system for the local delivery of antibiotics in the treatment of osteomyelitis.