Study of in situ forming sulfobutyl ether β-cyclodextrin/self-assembling peptide hydrogel and its release profile of dexamethasone in vitro
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1
University of Alberta, Department of Chemical and Materials Engineering, Canada
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2
National Research Council (Canada), National Institute for Nanotechnology, Canada
Introduction: The self-assembling peptide (RADA)4 is capable of forming bioactive scaffolds in situ for different biomedical applications. However, a universal way to control the delivery small hydrophobic drugs (ie. anti-inflammatory, anti-cancer, anti-bacterial drugs etc.) while maintaining a hydrogel structure is rarely reported. Cyclodextrins (CDs) have a relatively nonpolar cavity and a hydrophilic exterior, and have been used for solubilizing hydrophobic drugs in pharmaceutical applications for many years. Sulfobutyl ether β-cyclodextrin (SBE-β-CD; Captisol®) is a derivatized form of β-cyclodextrin with a range of six to seven sulfobutyl ether groups. In this work, the influence of SBE-β-CD on (RADA)4 peptide nanofiber conformation and the thermodynamic interactions between each molecule have been determined. A new strategy of using anionic SBE-β-CD as carrier to load hydrophobic drug in the peptide self-assembly nanofiber system is investigated.
Material and Methods: (RADA)4 peptide (≥95% purity) was purchased from RS Synthesis (USA). SBE-β-CD was donated by Ligand Pharmaceuticals, Inc. (USA). β-cyclodextrin (β-CD) and Dexamethasone (Dex) was purchased from Sigma (USA).
The influence of SBE-β-CD on peptide’s secondary structure and hydrogel formation was evaluated by AFM, circular dichroism (CD) and zeta potential analyzer. The binding affinities between model drug Dex, SBE-β-CD, and (RADA)4 was characterized using isothermal titration calorimetry (ITC). In vitro release of Dex from SBE-β-CD/(RADA)4 hydrogel was measure using UV-Vis.
Results and Discussion: The ionic interaction between SBE-β-CD and (RADA)4 peptide dramatically affects the nanofiber formation and subsequent gel stability; where gel stability is related to the SBE-β-CD/(RADA)4 ratio. Excessive amounts of SBE-β-CD seem to reduce the β-sheet formation of peptide, resulting in a white precipitation instead of transparent hydrogel. The ITC results suggest that the dissociation of SBE-β-CD/Dex inclusion complexes dominate the overall release rate. The different concentration of SBE-β-CD and (RADA)4 peptide significantly affect the release kinetics. Generally, higher concentration of both SBE-β-CD and (RADA)4 peptide is supposed to perform a slower release of drug. This observed phenomenon may related to the nanofiber cross-linking structure.
Conclusion: This work discussed the basis of the SBE-β-CD/self-assembling peptide based in situ hydrogel and leading to application prospects of other hydrophobic drugs delivery, such as anti-cancer or anti-infection therapies.
China Scholarship Council (CSC)
Keywords:
self-assembly,
Scaffold,
delivery,
gel
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Extracellular matrices for therapeutic delivery
Citation:
Lu
L and
Unsworth
LD
(2016). Study of in situ forming sulfobutyl ether β-cyclodextrin/self-assembling peptide hydrogel and its release profile of dexamethasone in vitro.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.01768
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.
*
Correspondence:
Dr. Lei Lu, University of Alberta, Department of Chemical and Materials Engineering, Edmonton, AB, Canada, Email1
Dr. Larry D Unsworth, University of Alberta, Department of Chemical and Materials Engineering, Edmonton, AB, Canada, larry.unsworth@ualberta.ca