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首页> 外文期刊>ChemMedChem >Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy
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Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy

机译:阳离子超分子水泡聚集体在抗癌治疗中的肺组织选择性递送。

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The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) by thin-layer evaporation and extrusion techniques. Both copolymers were self-assembled in pre-formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100nm. The anticancer activity of GEM-loaded neutral and cationic SVAs was tested in human alveolar basal epithelial (A549) and colorectal cancer (CaCo-2) cells. GEM-loaded cationic SVAs increased the anticancer activity in A549 and CaCo-2 cells relative to free drug, neutral SVAs, and CLs. Invivo biodistribution in Wistar rats showed that cationic SVAs accumulate at higher concentrations in lung tissue than neutral SVAs and CLs. Cationic SVAs may therefore serve as an innovative future therapy for pulmonary carcinoma.
机译:超分子水泡聚集体(SVA)的理化特性进行了表征,并与阳离子脂质体(CLs)进行了比较。使用聚天冬氨酰肼的两种不同共聚物,通过薄层蒸发和挤出技术合成了中性和阳离子型SVA。两种共聚物均在预配制的脂质体中自组装,并形成中性和阳离子SVA。盐酸吉西他滨(GEM)被用作抗癌药物,并通过pH梯度远程加载程序加载,这大大增加了SVA内部的药物加载。 SVA的平均尺寸为100nm。载有GEM的中性和阳离子型SVA的抗癌活性在人肺泡基底上皮(A549)和结直肠癌(CaCo-2)细胞中进行了测试。相对于游离药物,中性SVA和CL,载有GEM的阳离子SVA增强了A549和CaCo-2细胞的抗癌活性。 Wistar大鼠体内的体内生物分布表明,与中性SVA和CL相比,阳离子SVA在肺组织中的蓄积浓度更高。因此,阳离子SVA可以作为肺癌的一种创新的未来疗法。

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