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

Abstract

Cui Meng,1–3* Weipeng Wei,1,2* Yuhe Wang,1,3 Kunqin Zhang,1,2 Ting Zhang,1,2 Yunyan Tang,1,2 Fushan Tang1,2 1Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 2The Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi 563006, People’s Republic of China; 3Department of Pharmacy, The First Hospital Affiliated to Zunyi Medical University, Zunyi 563003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushan TangSchool of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaTel [phone]Email [email protected]: 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

Keywords

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