Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes.

Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes.
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DOI:
10.1021/mp3004379
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发表时间:
2012-11-05
影响因子:
4.9
通讯作者:
Cannon CL
Cannon CL
中科院分区:
医学2区
文献类型:
--
作者:
Ornelas-Megiatto C;Shah PN;Wich PR;Cohen JL;Tagaev JA;Smolen JA;Wright BD;Panzner MJ;Youngs WJ;Fréchet JM;Cannon CL

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制备了可降解的乙缩醛葡聚糖(Ac-DEX)纳米粒子,并用单乳液法将其负载于疏水的卡宾银络合物(SCC)中。用扫描电子显微镜、透射电子显微镜和动态光散射对所得颗粒的形貌和尺寸分布进行了表征。结果表明,当Ac-DEX-CH2Cl2(有机):PbS(水)的体积比为1:5时,制得的纳米粒子的平均粒径为100±40 nm,多分散性较低。研究发现,在颗粒配制过程中,随着初始原料中SCC用量的增加,SCC载量增加到30%(w/w);但在20%(w/w)的进料比例下,包封率最高。体外药效测试表明,载SCC的Ac-DEX纳米粒对革兰氏阴性菌和革兰氏阳性菌均有抑制作用;该纳米粒可抑制所有受试细菌的生长。正如预期的那样,当药物被包裹在纳米粒配方中时,与显示所需仓库释放的游离药物相比,需要更高浓度的药物来抑制细菌生长。与游离药物相比,Ac-DEX纳米粒更容易悬浮在水相中,随后被雾化,从而提供了一种有效的肺部给药方法。
Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH2Cl2 (organic): PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery.
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