Hassankhani Rad Ashkan, Asiaee Farshid, Jafari Sevda, Shayanfar Ali, Lavasanifar Afsaneh, Molavi Ommoleila
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz, Iran.
Bioimpacts. 2020;10(2):87-95. doi: 10.34172/bi.2020.11. Epub 2019 Nov 2.
Silibinin is a naturally occurring compound with known positive impacts on prevention and treatment of many types of in general and cancer in particular. Silibinin is poorly water soluble which results in its insufficient bioavailability and lack of therapeutic efficacy in cancer. Here, we proposed to examine the potential of micelles composed of poly(ethylene glycol) (PEG) as the hydrophilic block and poly(ε-caprolactone) (PCL), poly(α-benzylcarboxylate-ε-caprolactone) (PBCL), or poly(lactide)-(PBCL) (PLA-PBCL) as hydrophobic blocks for enhancing the water solubility of silibinin and its targeted delivery to tumor. Co-solvent evaporation method was used to incorporate silibinin into PEG-PCL based micelles. Drug release profiles were assessed using dialysis bag method. MTT assay also was used to analyze functional activity of drug delivery in B16 melanoma cells. Silibinin encapsulated micelles were shown to be less than 60 nm in size. Among different structures under study, the one with PEG-PBCL could incorporate silibinin with the highest encapsulation efficiency being 95.5%, on average. PEG-PBCL micelles could solubilize 1 mg silibinin in 1 mL water while the soluble amount of silibinin was found to be 0.092 mg/mL in the absence of polymeric micelles. PEG-PBCL micelles provided the sustained release of silibinin indicated with less than 30% release of silibinin within 24 hours. Silibinin encapsulated in PEG-PBCL micelles resulted in growth inhibitory effect in B16 cancer cells which was significantly higher than what observed with free drug. Our findings showed that PEG-PBCL micellar nanocarriers can be a useful vehicle for solubilization and targeted delivery of silibinin.
水飞蓟宾是一种天然存在的化合物，总体上对多种疾病的预防和治疗具有积极作用，尤其是对癌症。水飞蓟宾的水溶性较差，这导致其生物利用度不足，在癌症治疗中缺乏疗效。在此，我们提议研究由聚乙二醇（PEG）作为亲水嵌段和聚（ε-己内酯）（PCL）、聚（α-苄基羧酸酯-ε-己内酯）（PBCL）或聚（丙交酯）-（PBCL）（PLA-PBCL）作为疏水嵌段组成的胶束，以提高水飞蓟宾的水溶性及其向肿瘤的靶向递送。采用共溶剂蒸发法将水飞蓟宾掺入基于PEG-PCL的胶束中。使用透析袋法评估药物释放曲线。MTT法也用于分析药物递送在B16黑色素瘤细胞中的功能活性。包封有水飞蓟宾的胶束尺寸小于60nm。在所研究的不同结构中，PEG-PBCL组成的胶束平均包封效率最高，可达95.5%，能将水飞蓟宾掺入其中。PEG-PBCL胶束可在1mL水中溶解1mg水飞蓟宾，而在没有聚合物胶束的情况下，水飞蓟宾的可溶量为0.092mg/mL。PEG-PBCL胶束实现了水飞蓟宾的持续释放，24小时内水飞蓟宾的释放量不到30%。包封在PEG-PBCL胶束中的水飞蓟宾对B16癌细胞产生生长抑制作用，显著高于游离药物的作用效果。我们的研究结果表明，PEG-PBCL胶束纳米载体可成为水飞蓟宾增溶和靶向递送的有用载体。
