Cationic liposomes as carriers for aerosolized formulations of an anionic drug: safety and efficacy study.
Cationic liposomes as carriers for aerosolized formulations of an anionic drug: safety and efficacy study.
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DOI：
10.1016/j.ejps.2009.07.002
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发表时间：
2009-09-10
影响因子：
4.6
通讯作者：
Ahsan, Fakhrul
中科院分区：
文献类型：
--
作者：
Bai, Shuhua;Gupta, Vivek;Ahsan, Fakhrul
关键词：
本研究检验了聚乙二醇化阳离子脂质体是低分子量肝素（一种阴离子药物）可吸入制剂的可行载体的假设。使用1，2-二油酰基-3-三甲基铵-丙烷（氯化物盐）、胆固醇和1，2-二硬脂酰基-sn-甘油基-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇）-2000]，通过水合法制备低分子量肝素的阳离子脂质体制剂。制剂的特征在于粒径，包封率，肺吸收和药理学功效。对于吸收研究，将制剂通过肺途径给予麻醉的雄性Sprague-Dawley大鼠，并通过测量血浆抗因子Xa活性监测药物吸收。在肺栓塞和深静脉血栓形成的啮齿动物模型中研究了制剂的药理学功效。脂质体平均粒径为104.8± 20.7nm，包封率为90.3± 0.1%。阳离子脂质体制剂的半衰期为10.6±0.2 h，与生理盐水中配制的低分子量肝素相比增加了2.2倍，与皮下给药药物相比，相对生物利用度为73.4±19.1%。隔日一次吸入剂量的制剂在降低血栓重量方面显示出与每日一次皮下给药药物相似的疗效。同样，在肺栓塞前6小时通过肺途径给予阳离子脂质体制剂显示出与栓塞前2小时皮下给予低分子量肝素相当的溶栓作用。肺组织的组织学检查和支气管肺泡灌洗液中损伤标志物的测量表明，制剂未产生广泛的损伤。结果表明，聚乙二醇化的阳离子脂质体可能是低分子量肝素可吸入制剂的可行载体。
This study tests the hypothesis that pegylated cationic liposomes are a viable carrier for inhalable formulations of low molecular weight heparin, an anionic drug. Cationic liposomal formulations of low molecular weight heparin were prepared by the hydration method using 1,2-dioleoyl-3-trimethylammonium-propane (chloride salt), cholesterol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]. The formulations were characterized for particle size, entrapment efficiency, pulmonary absorption and pharmacological efficacy. For absorption studies, the formulations were administered to anesthetized male Sprague-Dawley rats via the pulmonary route and drug absorption was monitored by measuring plasma anti-factor Xa activity. The pharmacological efficacy of the formulations was studied in rodent models of pulmonary embolism and deep vein thrombosis. The mean particle size of the liposomes was 104.8±20.7 nm and the drug entrapment efficiency was 90.3±0.1%. The half-life of the cationic liposomal formulation was 10.6±0.2 h, a 2.2-fold increase compared to low molecular weight heparin formulated in saline, and the relative bioavailability was ∼73.4±19.1% when compared to subcutaneously administered drug. A once-every-other-day inhaled dose of the formulation showed similar efficacy in reducing thrombus weight as a once-daily dose of subcutaneously administered drug. Likewise, cationic liposomal formulations administered via the pulmonary route 6 h prior to embolization in the lungs showed a thrombolytic effect comparable to that of low molecular weight heparin administered subcutaneously 2 h before embolization. Histological examination of lung tissue and measurement of injury markers in bronchoalveolar lavage fluid suggest that the formulations did not produce extensive damage. The results demonstrate that pegylated cationic liposomes could be a viable carrier for an inhalable formulation of low molecular weight heparin.
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影响因子：
3.8
作者：
Bai, Shuhua;Thomas, Chandan;Ahsan, Fakhrul
通讯作者：
Ahsan, Fakhrul
影响因子：
10.8
作者：
Yang, Tianzhi;Hussain, Alamdar;Ahsan, Fakhrul
通讯作者：
Ahsan, Fakhrul
DOI：
10.1073/pnas.85.18.6949
发表时间：
1988-09-01
影响因子：
11.1
作者：
GABIZON, A;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
影响因子：
3.7
作者：
Bai, Shuhua;Ahsan, Fakhrul
通讯作者：
Ahsan, Fakhrul
影响因子：
3.3
作者：
Yang, TZ;Mustafa, F;Ahsan, F
通讯作者：
Ahsan, F