Gentamicin-loaded nanoparticles show improved antimicrobial effects towards Pseudomonas aeruginosa infection.
Gentamicin-loaded nanoparticles show improved antimicrobial effects towards Pseudomonas aeruginosa infection.
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DOI：
10.2147/ijn.s34341
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发表时间：
2012
影响因子：
8
通讯作者：
Scott CJ
中科院分区：
文献类型：
--
作者：
Abdelghany SM;Quinn DJ;Ingram RJ;Gilmore BF;Donnelly RF;Taggart CC;Scott CJ
庆大霉素是一种氨基糖苷类抗生素，常用于治疗假单胞菌感染，但其使用受到半衰期相对较短的限制。在这项研究中，开发了一种控制释放庆大霉素制剂使用聚（丙交酯-共-乙交酯）（PLGA）纳米粒子。我们证明，亲水性药物包埋到疏水性PLGA聚合物中可以通过增加制剂的pH值来改善，降低药物的亲水性，从而增强包埋，达到高达22.4 μg/mg PLGA的水平。在标准孵育条件下，这些颗粒显示出庆大霉素的受控释放长达16天。在体外以及在96小时腹膜鼠感染模型中，针对铜绿假单胞菌PA 01的渗透性和生物膜培养物测试这些颗粒。在该模型中，颗粒引起显著改善的抗微生物作用，如通过与96小时的游离药物给药相比，较低的血浆和腹膜灌洗集落形成单位以及替代炎症指标白细胞介素-6和髓过氧化物酶的相应减少所确定的。这些数据强调庆大霉素的控释可能适用于治疗假单胞菌感染。
Gentamicin is an aminoglycoside antibiotic commonly used for treating Pseudomonas infections, but its use is limited by a relatively short half-life. In this investigation, developed a controlled-release gentamicin formulation using poly(lactide-co-glycolide) (PLGA) nanoparticles. We demonstrate that entrapment of the hydrophilic drug into a hydrophobic PLGA polymer can be improved by increasing the pH of the formulation, reducing the hydrophilicity of the drug and thus enhancing entrapment, achieving levels of up to 22.4 μg/mg PLGA. Under standard incubation conditions, these particles exhibited controlled release of gentamicin for up to 16 days. These particles were tested against both planktonic and biofilm cultures of P. aeruginosa PA01 in vitro, as well as in a 96-hour peritoneal murine infection model. In this model, the particles elicited significantly improved antimicrobial effects as determined by lower plasma and peritoneal lavage colony-forming units and corresponding reductions of the surrogate inflammatory indicators interleukin-6 and myeloperoxidase compared to free drug administration by 96 hours. These data highlight that the controlled release of gentamicin may be applicable for treating Pseudomonas infections.