Characterization of a reverse-phase perfluorocarbon emulsion for the pulmonary delivery of tobramycin.
Characterization of a reverse-phase perfluorocarbon emulsion for the pulmonary delivery of tobramycin.
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用于肺部输送妥布霉素的反相全氟化碳乳液的表征。
DOI：
10.1089/jamp.2013.1058
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发表时间：
2014
影响因子：
3.4
通讯作者：
Cook,KeithE
中科院分区：
文献类型：
--
作者：
Orizondo,RyanA;Babcock,CharleneIrvin;Fabiilli,MarioL;Pavlovsky,Leonid;Fowlkes,JBrian;Younger,JohnG;Cook,KeithE
背景：抗生素雾化递送由于远端气道渗透不良和堵塞而受到阻碍。抗菌全氟碳通气（APV）是一种将含有乳化抗生素的全氟碳（PFC）部分或全部填充肺部的拟议解决方案。本研究的目的是评价乳剂的稳定性、流变学、抗菌和药代动力学特性。方法：研究了24小时内乳状液水滴直径、数密度以及乳状液和纯PFC的粘度和表面张力。此外，在不同水体积百分比（0.25、1和2.5%）和妥布霉素水浓度（Ca=0.4、4和40 mg/mL）的乳剂中暴露2小时后，测量铜绿假单胞菌的生长情况。最后，评估大鼠在APV和常规雾化给药后血清和肺部妥布霉素浓度的时间过程。结果：水滴初始直径平均为1.9±0.2 μm，随时间变化不大。初始水滴数密度平均为3.5±1.7×109droplets/mL，随时间的推移显著降低（p<0.01）。乳化液和PFC粘度无显著差异，平均为1.22±0.03×10-3Pa·sec。PFC和乳液的表面张力分别为15.0±0.1×10-3and 14.6±0.6×10-3N /m，水界面张力分别为46.7±0.3×10-3and 26.9±11.0×10-3N /m （p<0.01）。随着水体积百分比的增加，生物膜的生长明显下降，并且在较小程度上影响水体积百分比。经APV给药的妥布霉素在给药后1小时和4小时的肺浓度分别是雾化给药的2.5倍和10倍，血清浓度显著低于雾化给药（p<0.05）。结论：乳剂具有杀菌作用，保留了肺输送所需的流变性，在此应用中具有足够的稳定性，并导致抗生素的肺潴留增加。
Background:Aerosolized delivery of antibiotics is hindered by poor penetration within distal and plugged airways. Antibacterial perfluorocarbon ventilation (APV) is a proposed solution in which the lungs are partially or totally filled with perfluorocarbon (PFC) containing emulsified antibiotics. The purpose of this study was to evaluate emulsion stability and rheological, antibacterial, and pharmacokinetic characteristics.Methods:This study examined emulsion aqueous droplet diameter and number density over 24 hr and emulsion and neat PFC viscosity and surface tension. Additionally,Pseudomonas aeruginosabiofilm growth was measured after 2-hr exposure to emulsion with variable aqueous volume percentages (0.25, 1, and 2.5%) and aqueous tobramycin concentrations (Ca=0.4, 4, and 40 mg/mL). Lastly, the time course of serum and pulmonary tobramycin concentrations was evaluated following APV and conventional aerosolized delivery of tobramycin in rats.Results:The initial aqueous droplet diameter averaged 1.9±0.2 μm with little change over time. Initial aqueous droplet number density averaged 3.5±1.7×109droplets/mL with a significant (p<0.01) decrease over time. Emulsion and PFC viscosity were not significantly different, averaging 1.22±0.03×10–3Pa·sec. The surface tensions of PFC and emulsion were 15.0±0.1×10–3and 14.6±0.6×10–3N/m, respectively, and the aqueous interfacial tensions were 46.7±0.3×10–3and 26.9±11.0×10–3N/m (p<0.01), respectively. Biofilm growth decreased markedly with increasingCaand, to a lesser extent, aqueous volume percentage. Tobramycin delivered via APV yielded 2.5 and 10 times larger pulmonary concentrations at 1 and 4 hr post delivery, respectively, and significantly (p<0.05) lower serum concentrations compared with aerosolized delivery.Conclusions:The emulsion is bactericidal, retains the rheology necessary for pulmonary delivery, is sufficiently stable for this application, and results in increased pulmonary retention of the antibiotic.
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DOI：
10.1164/ajrccm.165.6.2003052
发表时间：
2002-03-15
影响因子：
24.7
作者：
Hirschl, RB;Croce, M;Bartlett, RH
通讯作者：
Bartlett, RH
影响因子：
4.9
作者：
OMRI, A;BEAULAC, C;LAGACE, J
通讯作者：
LAGACE, J
使用全氟龙递送的妥布霉素预防 rts 中的下行肺炎。
DOI：
10.1197/s1069-6563(03)00335-x
发表时间：
2003
期刊：
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
影响因子：
--
作者：
E. Dickson;G. Doern;L. Trevino;M. Mazzoni;S. Heard
通讯作者：
S. Heard
影响因子：
3.1
作者：
Yildizeli, B;Zonüzi, F;Küllü, S
通讯作者：
Küllü, S
影响因子：
2.9
作者：
Kripfgans, OD;Fowlkes, JB;Carson, PL
通讯作者：
Carson, PL