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Minocycline and Silver Dual-Loaded Polyphosphoester-Based Nanoparticles for Treatment of Resistant Pseudomonas aeruginosa
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-02-28 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b01288
Qingquan Chen 1 , Kush N. Shah 1 , Fuwu Zhang 2 , Adam J. Salazar 3 , Parth N. Shah 1 , Richen Li 2 , James C. Sacchettini 3 , Karen L. Wooley 2 , Carolyn L. Cannon 1
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-02-28 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b01288
Qingquan Chen 1 , Kush N. Shah 1 , Fuwu Zhang 2 , Adam J. Salazar 3 , Parth N. Shah 1 , Richen Li 2 , James C. Sacchettini 3 , Karen L. Wooley 2 , Carolyn L. Cannon 1
Affiliation
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Pseudomonas aeruginosa has been detected in the lungs of ∼50% of patients with cystic fibrosis (CF), including 20% of adult CF patients. The majority of these adult patients harbor multi-drug resistant (MDR) strains, limiting the available treatment options. Silver has long been used as a broad-spectrum antimicrobial agent with a low incidence of resistance. Despite low toxicity, poor availability of silver cations mandates a high dosage to effectively eradicate infections. To address this shortcoming of silver, nanoparticles have been used as delivery devices to improve treatment outcomes. Furthermore, studies have demonstrated that synergistic combinations with careful dose calibrations and efficient delivery systems result in superior antimicrobial activity while avoiding potential side effects of both therapeutics. Here 4-epi-minocycline, a metabolite of minocycline, was identified as an active antimicrobial against P. aeruginosa using a high-throughput screen. The antimicrobial activities of 4-epi-minocycline, minocycline, and silver acetate against clinical isolates of P. aeruginosa obtained from CF patients were evaluated in vitro. Next, the synergistic activity of the silver/minocycline combination against P. aeruginosa isolates was investigated using checkerboard assays and identified with end-point colony forming unit determination assays. Finally, nanoparticles coloaded with minocycline and silver were evaluated in vitro for antimicrobial activity. The results demonstrated that both silver and minocycline are potent antimicrobials alone and that the combination allows a reduced dosage of both therapeutics to achieve the same antimicrobial effect. Furthermore, the proposed synergistic silver/minocycline combination can be coloaded into nanoparticles as a next-generation antibiotic to combat the threats presented by MDR pathogens.
中文翻译：
Minocycline和银双负载基于聚磷酸酯的纳米粒子治疗抗铜绿假单胞菌
铜绿假单胞菌已在约50％的囊性纤维化（CF）患者的肺中检测到这种病毒，其中20％的成人CF患者。这些成年患者中的大多数都携带多药耐药性（MDR）株，从而限制了可用的治疗选择。长期以来，银一直被用作抗药性低的广谱抗菌剂。尽管毒性低，但是银阳离子的利用率差，要求高剂量才能有效根除感染。为了解决银的这一缺点，纳米颗粒已被用作递送装置以改善治疗效果。此外，研究表明，精心组合的剂量校准和有效的输送系统的协同组合可产生出色的抗菌活性，同时避免了两种疗法的潜在副作用。这里是4-表-氨基环素，使用高通量筛选的铜绿假单胞菌。在体外评价了4-表-米诺环素，米诺环素和乙酸银对从CF患者获得的铜绿假单胞菌临床分离株的抗菌活性。接下来，银/米诺环素组合物对铜绿假单胞菌的协同活性使用棋盘试验对分离的菌株进行了研究，并通过终点菌落形成单位测定分析进行了鉴定。最后，在体外评估了与米诺环素和银共载的纳米颗粒的抗菌活性。结果表明，银和米诺环素均是有效的抗菌剂，并且该组合可减少两种疗法的剂量，以达到相同的抗菌效果。此外，可以将拟议的协同银/米诺环素组合物作为下一代抗生素共装载到纳米颗粒中，以对抗MDR病原体带来的威胁。
更新日期：2019-02-28
中文翻译：
Minocycline和银双负载基于聚磷酸酯的纳米粒子治疗抗铜绿假单胞菌
铜绿假单胞菌已在约50％的囊性纤维化（CF）患者的肺中检测到这种病毒，其中20％的成人CF患者。这些成年患者中的大多数都携带多药耐药性（MDR）株，从而限制了可用的治疗选择。长期以来，银一直被用作抗药性低的广谱抗菌剂。尽管毒性低，但是银阳离子的利用率差，要求高剂量才能有效根除感染。为了解决银的这一缺点，纳米颗粒已被用作递送装置以改善治疗效果。此外，研究表明，精心组合的剂量校准和有效的输送系统的协同组合可产生出色的抗菌活性，同时避免了两种疗法的潜在副作用。这里是4-表-氨基环素，使用高通量筛选的铜绿假单胞菌。在体外评价了4-表-米诺环素，米诺环素和乙酸银对从CF患者获得的铜绿假单胞菌临床分离株的抗菌活性。接下来，银/米诺环素组合物对铜绿假单胞菌的协同活性使用棋盘试验对分离的菌株进行了研究，并通过终点菌落形成单位测定分析进行了鉴定。最后，在体外评估了与米诺环素和银共载的纳米颗粒的抗菌活性。结果表明，银和米诺环素均是有效的抗菌剂，并且该组合可减少两种疗法的剂量，以达到相同的抗菌效果。此外，可以将拟议的协同银/米诺环素组合物作为下一代抗生素共装载到纳米颗粒中，以对抗MDR病原体带来的威胁。
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