Kanamycin incorporation in lipid vesicles prepared by ethanol injection designed for tuberculosis treatment
Kanamycin incorporation in lipid vesicles prepared by ethanol injection designed for tuberculosis treatment
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DOI：
10.1211/0022357055092
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Moraes, AM
中科院分区：
文献类型：
--
作者：
Justo, OR;Moraes, AM
本研究的主要目标是生产封装卡那霉素的脂质体，用于吸入给药。所选药物适用于耐多药结核病，通过吸入给药既可以将药物局部输送到肺部，也可以进行全身治疗。用于脂质体生产的乙醇注射法易于放大，具有简单、成本低的特点。使用不同的脂质组合物制备囊泡，包括氢化大豆磷脂酰胆碱和胆固醇（SPC/Chol）、鸡蛋磷脂酰胆碱和胆固醇（EPC/Chol）、二硬脂酰磷脂酰胆碱和胆固醇（DSPC/Chol）、二硬脂酰磷脂酰胆碱、二肉豆蔻酰磷脂酰乙醇胺和胆固醇（DSPC）DME/Chol）、二棕榈酰磷脂酰胆碱和胆固醇(DPPC/Chol)和二棕榈酰磷脂酰胆碱、二棕榈酰磷脂酰甘油和胆固醇(DPPC/DPPG/Chol)。评估了不同操作条件对囊泡生产和药物封装的影响，旨在最终工艺成本和合适的囊泡特性之间取得折衷。尽管其生产成本比天然脂质制剂高得多，但 DSPC/Chol 系统在药物掺入方面取得了最佳性能。对于平均直径为 132 nm 的 SPC/Chol 囊泡，在 60°C 下与药物一起孵育 60 分钟，初始药物与脂质摩尔比为 0.16，包封效率高达 63%，最终药物与脂质摩尔比高达 0.1。
The primary goal of this study was the production of liposomes encapsulating kanamycin for drug administration by inhalation. The selected drug is indicated for multiresistant tuberculosis, and administration through inhalation allows both local delivery of the drug to the lungs and systemic therapy. The ethanol injection method used for the liposome production is easily scaled up and is characterized by simplicity and low cost. Vesicles were prepared using different lipid compositions, including hydrogenated soybean phosphaticlylcholine and cholesterol (SPC/Chol), egg phoshatioylcholine and cholesterol (EPC/Chol), distearoyl phosphatidylcholine and cholesterol (DSPC/Chol), distearoyl phosphaticlylcholine, dimyristoyl phosphatidylethanolamine and cholesterol (DSPC)DME/ Chol), dipalmitoyl phosphaticlylcholine and cholesterol (DPPC/Chol) and dipalmitoyl phosphatioylcholine, dipalmitoyl phosphatidylglycerol and cholesterol (DPPC/DPPG/Chol). The effects of different operational conditions for vesicle production and drug encapsulation were evaluated, aiming at a compromise between final process cost and suitable vesicle characteristics. The best performance concerning drug incorporation was achieved with the DSPC/Chol system, although it production cost was considerably larger than that of the natural lipids formulations. Encapsulation efficiencies up to 63% and final drug to lipid molar ratios up to 0.1 were obtained for SPC/Chol vesicles presenting mean diameters of 132 nm incubated at 60degreesC with the drug for 60 min at an initial drug-to-lipid molar ratio of 0.16.