Study of the interaction between self-assembling peptide and mangiferin and in vitro release of mangiferin from in situ hydrogel

Abstract

Objective

This study aimed to investigate the interaction between the ion-complementary self-assembling peptide RADA16-I and the hydrophobic drug mangiferin (MA), and the potential of the self-assembling peptide to be exploited as a drug carrier of MA.

Methods

The RADA16-I–MA suspension was prepared by magnetic stirring, followed by fluorescence spectrophotometry, particle size determination, rheological properties analysis, and in vitro release assay to characterize the interaction between RADA16-I and MA. Then, the effects of in situ MA-loaded hydrogel on the proliferation of KYSE 30 and DLD-1 tumor cells and the toxic effect of the hydrogel on 293T renal epithelial cells were studied by the Cell Counting Kit 8 method.

Results

The RADA16-I–MA suspension was formed in water under magnetic stirring; the in situ hydrogel was formed when the suspension was added to PBS. The particle size in the RADA16-I–MA suspension was around 300–600 nm with an average size of 492 nm. Within 24 h, the cumulative release of MA from the RADA16-I–MA hydrogel was about 80%. The release rate of MA from the hydrogel was dependent on the concentration of RADA16-I and the release can be fitted with a first-order kinetic equation. The results suggested that the self-assembling peptide can stabilize MA in water to form a relatively stable suspension; the results also indicated that controlled release of MA from the RADA16-I–MA in situ hydrogel formed from the RADA16-I–MA suspension can be achieved by adjusting the concentration of the peptide in suspension. The cell viability studies showed that the RADA16-I–MA in situ hydrogel not only can maintain or enhance the intrinsic proliferation inhibition effects of MA on tumor cells, but also can reduce the toxicity of MA to normal cells.

Conclusion

The self-assembling peptide RADA16-I can be a potential candidate for constructing a delivery system of the hydrophobic drug MA.

Keywords:

• RADA16-I
• hydrophobic drug
• delivery system
• antitumor

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No. 31460246), the 2011 Collaborative Innovation Center of Guizhou Traditional Chinese Medicine and Ethnic Medicine (No. Qianjiaokeyanfa (2012) 311), the Education Department of Guizhou Province of China (No. GNYL (2017) 006 and YLXKJS-YS-05), and the Guizhou Provincial and Municipal Science and Technology Cooperation Special Fund Project (No. Shengshikehe (2015) 53). Great thanks goes to the Army Medical University School of Pharmaceutics for rheological measurement and to the State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College for cell experiments.

Disclosure

The authors report no conflicts of interest in this work.