Design and Toxicity Evaluation of Novel Fatty Acid-Amino Acid-Based Biocompatible Surfactants
Design and Toxicity Evaluation of Novel Fatty Acid-Amino Acid-Based Biocompatible Surfactants
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DOI：
10.1208/s12249-019-1396-x
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发表时间：
2019-05
影响因子：
3.3
通讯作者：
S. Katiyar;Varun Kushwah;C. Dora;R. Patil;Sanyog Jain
中科院分区：
文献类型：
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作者：
S. Katiyar;Varun Kushwah;C. Dora;R. Patil;Sanyog Jain
表面活性剂由于其广泛的应用而占有重要的地位，但主要由于其毒性问题而受到损害。这就需要探索具有更高生物相容性的新型表面活性剂。采用标准碳二亚胺化学方法制备了新型脂肪酸基和氨基酸基表面活性剂。用芘测定法确定了表面活性剂的两亲性，并计算了临界胶束浓度。对MCF-7和HEK细胞株进行了体外溶血和细胞培养研究，以比较所开发的表面活性剂与市场上销售的表面活性剂Triton X-100和Tween®80的体外生物相容性。在瑞士雌性白化病小鼠体内进行了生物相容性试验，与市售表面活性剂在血清标志物、器官组织学和红细胞形态学方面进行了比较。表面活性剂合成的共轭物产率均在60%以上。在硬脂酸和缬氨酸偶联物的情况下，表面活性剂具有两亲性，CMC最低为0.083% w/v。体外溶血和细胞培养研究表明，与市场上销售的表面活性剂相比，体外生物相容性最高。与市场上销售的表面活性剂Triton X-100和Tween®80相比，在AST（天冬氨酸转氨酶）、ALT（丙氨酸转氨酶）、BUN（血尿素氮）、血清肌酐水平和脾脏、肝脏和肾脏组织学方面获得了相似的体内生物相容性。所研制的表面活性剂在体内红细胞形态变化最小。硬脂酸缬氨酸缀合物因此描绘了在配方开发中取代市售表面活性剂的进一步应用潜力。
Surfactants occupy an important place owing to their wide application, but primarily compromised due to its toxicity issues. This raises the need for exploration of newer surfactants with increased biocompatibility. Novel fatty acid- and amino acid-based surfactants were prepared using standard carbodiimide chemistry. Pyrene assay was implemented to confirm the amphiphilic nature of the surfactants and to calculate their CMC (critical micellar concentration). In vitro hemolytic and cell culture study in MCF-7 and HEK cell line were done to check the in vitro biocompatibility of the developed surfactants in comparison to marketed surfactants Triton X-100 and Tween ® 80. In vivo biocompatibility test in female Swiss albino mice was carried out in comparison to marketed surfactants with respect to serum markers, organ histology, and RBC morphology. Surfactant synthesis provided more than 60% yield in all the conjugates. Pyrene assay concluded the amphiphilic nature of the surfactants with lowest CMC of 0.083% w/v in the case of stearic acid and valine conjugate. In vitro hemolytic and cell culture study depicted highest biocompatibility in vitro as compared to marketed surfactants. Similar results were obtained in in vivo biocompatibility with respect to AST (aspartate transaminase), ALT (alanine transaminase), BUN (blood urea nitrogen), and creatinine serum levels and histology of spleen, liver, and kidney in comparison to marketed surfactants Triton X-100 and Tween ® 80. The developed surfactant also depicted least RBC morphology changes in vivo. Stearic acid valine conjugate thus depicted potential for further application in formulation development replacing the commercially available surfactants.