Effects of fluorosurfactant structure and concentration on drug availability and biocompatibility in water-in-perfluorocarbon emulsions for pulmonary drug delivery
Effects of fluorosurfactant structure and concentration on drug availability and biocompatibility in water-in-perfluorocarbon emulsions for pulmonary drug delivery
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含氟表面活性剂结构和浓度对全氟化碳包水乳剂肺部给药药物利用度和生物相容性的影响
DOI：
10.1007/s00396-017-4216-4
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发表时间：
2017
影响因子：
2.4
通讯作者：
K. Cook
中科院分区：
文献类型：
--
作者：
Ryan A. Orizondo;Diane L. Nelson;M. Fabiilli;K. Cook
吸入抗生素的疗效往往因药物对堵塞和通风不良的呼吸道的渗透不足而受到损害。使用含乳化水抗生素的全氟化碳(PFC)进行液体通风，或使用抗菌全氟碳通风，作为吸入抗生素的辅助治疗，可能会改善呼吸道感染的治疗。用于稳定这种PFC水乳剂的氟表面活性剂的分子结构和浓度将对所产生的处理的有效性和安全性产生重大影响。在本研究中，在不同浓度(CFs)的两种不同的含氟表面活性剂(称为FSL-PEG+FSL和FSH-PEG)的水相中，用妥布霉素配制乳剂。水凝胶用于评估乳化药物在不同乳剂配方中扩散到水界面(如粘液或生物膜)的有效性。最后，用人肺泡基底上皮细胞表征了含氟表面活性剂的细胞毒性。结果表明，妥布霉素在低CFS时由于药物乳化不足而减少，而在大CFS时则由于药物可利用度受阻而减少。因此，对于FSH-聚乙二醇和FSL-聚乙二醇+FSL氟表面活性剂，在CFs的中间值分别等于2和10 mg/mLFs1时，出现最大释放。优化的乳剂配方使用了FSH-聚乙二醇酯，与以前使用的配方相比，表现出更好的药物释放性能，同时没有细胞毒性作用。这项工作增加了对通过PFC水包水乳剂给药的物理手段的了解，并代表了优化乳剂配方以实现安全和有效治疗的关键一步。
The efficacy of inhaled antibiotics is often impaired by insufficient drug penetration into plugged and poorly ventilated airways. Liquid ventilation with perfluorocarbon (PFC) containing emulsified aqueous antibiotics, or antibacterial perfluorocarbon ventilation, could potentially improve treatment of respiratory infections when used as an adjunct therapy to inhaled antibiotics. The molecular structure and concentration of the fluorosurfactant used to stabilize such water-in-PFC emulsions will have significant effects on the efficacy and safety of the resulting treatment. In the present study, emulsions are formulated with tobramycin in the aqueous phase using two different fluorosurfactants (termed FSL-PEG+FSL and FSH-PEG) at varying concentrations (Cfs). An aqueous gel is used to evaluate the availability of emulsified drug to diffuse into an aqueous interface (such as mucus or biofilm) for varying emulsion formulations. Lastly, the cytotoxicity of the fluorosurfactants is characterized using human alveolar basal epithelial cells. Results showed that tobramycin delivery is reduced at low Cfs due to inadequate drug emulsification and at large Cfs due to hindered drug availability. Thus, maximal delivery occurs at intermediate values of Cfs equal to 2 and 10 mg mL−1 for the FSH-PEG and FSL-PEG+FSL fluorosurfactants, respectively. The optimal emulsion formulation utilized FSH-PEG and demonstrated improved drug delivery relative to previously used formulations while exhibiting no cytotoxic effect. This work increases understanding of the physical means of pulmonary drug delivery via a water-in-PFC emulsion and represents a critical step in optimizing emulsion formulation for safe and effective treatment.
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定量房水中环丙沙星和妥布霉素的生物测定。
DOI：
10.1089/jop.1993.9.311
发表时间：
1993
期刊：
Journal of ocular pharmacology
影响因子：
--
作者：
Engel,LS;Callegan,MC;Hill,JM;O'Callaghan,RJ
通讯作者：
O'Callaghan,RJ
用于肺部输送妥布霉素的反相全氟化碳乳液的表征。
影响因子：
3.4
作者：
Orizondo,RyanA;Babcock,CharleneIrvin;Fabiilli,MarioL;Pavlovsky,Leonid;Fowlkes,JBrian;Younger,JohnG;Cook,KeithE
通讯作者：
Cook,KeithE
液体通气可在呼吸衰竭的情况下提供全氟化碳的均匀分布。
影响因子：
3.8
作者：
Hirschl,RB;Overbeck,MC;Parent,A;Hernandez,R;Schwartz,S;Dosanjh,A;Johnson,K;Bartlett,RH
通讯作者：
Bartlett,RH
影响因子：
6.1
作者：
Holtze, C.;Rowat, A. C.;Weitz, D. A.
通讯作者：
Weitz, D. A.