Design and Toxicity Evaluation of Novel Fatty Acid-Amino Acid-Based Biocompatible Surfactants

Abstract

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.

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Acknowledgements

The authors are thankful to the Ministry of Chemicals and Fertilizers, Govt. of India, and Director NIPER S.A.S. Nagar for providing fellowship and funding for the proposed work. Authors also want to express their thanks to NIPER S.A.S. Nagar for providing necessary benefits. Varun Kushwah is thankful to CSIR, Govt. of India, and Chander Parkash Dora is thankful to UGC, Govt. of India, for providing research fellowship.

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Correspondence to Sanyog Jain.

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The animal protocol was duly approved by the Institutional Animal Ethics Committee, NIPER (IAEC) and studies were carried out according to the CPCSEA guidelines.

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Katiyar, S.S., Kushwah, V., Dora, C.P. et al. Design and Toxicity Evaluation of Novel Fatty Acid-Amino Acid-Based Biocompatible Surfactants. AAPS PharmSciTech 20, 186 (2019). https://doi.org/10.1208/s12249-019-1396-x

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KEY WORDS

  • amino acid
  • fatty acid
  • surfactants
  • toxicity
  • biocompatibility