Protein structure and bioactivity upon adsorption and desorption from nanosilicate sustained release delivery devices

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Sustained local delivery of biologics using hydrogel carriers is crucial for enhancing protein safety and efficacy.
• Incorporating nanoparticles into hydrogels improves the retention and release kinetics of biologics.
• Nanosilicates, like LAPONITE® XLG (NS), offer high surface area for complexing biologics, enabling tunable release profiles.

Purpose of the Study:

• To investigate the structure and stability of nanosilicate-protein complexes.
• To evaluate protein activity and structural changes upon complexation with nanosilicate.
• To understand the interactions between proteins and nanosilicate for advanced drug delivery applications.

Main Methods:

• Binding affinity assays to determine protein-nanosilicate interactions.
• Spectroscopic methods to assess protein structure and unfolding.
• Bioactivity assays to measure protein function post-complexation and release.
• Analysis of protein stability in the presence of denaturants.

Main Results:

• Strong correlation observed between protein charge and binding affinity to NS, with positively charged proteins showing higher attraction.
• Proteins exhibited temporary unfolding and partial bioactivity loss in solution with NS.
• Released proteins from PEG-NS hydrogels demonstrated recovery of secondary structure and bioactivity.
• Nanosilicate binding offered partial protection against the denaturant guanidine thiocyanate.

Conclusions:

• Nanosilicate-protein complexation influences protein structure and activity, but this is reversible upon release from hydrogels.
• Understanding these interactions is key to developing NS-based hydrogels for tunable, sustained biologic delivery.
• This study supports the use of NS-protein complexes as effective components in advanced drug delivery devices.