Aldehyde-Modified Hyaluronic Acid Hydrogel with Immobilized Polyelectrolyte Complexes of Aldehyde-Modified Chondroitin Sulfate: An in Situ Approach for Synthetic Preimplantation Factor Delivery

Abstract

This study introduces an injectable Drug Delivery System (DDS) for Multiple Sclerosis treatment utilizing aldehyde-modified hyaluronic acid (HAOX) and chondroitin sulfate (CSOX) to deliver FITC-modified Synthetic Preimplantation Factor (FITC-SPIF). The developed system formed a crosslinked polymer network using O,O′-1,3-propanediylbishydroxylamine (PDHA) as the crosslinker with polyelectrolyte complexes (PEC) of CSOX and FITC-SPIF immobilized on the system. The electrostatic attraction between the negatively charged sulfate group of CSOX and the positively charged amino acids of FITC-SPIF can be used as an entrapment strategy to avoid the application of toxic crosslinking agents. This DDS, which crosslinks and gels within minutes, can be injected through a 27 G needle, ensures minimal leakage and seamlessly integrates with implanted devices to enable controlled drug release via anomalous diffusion. Increasing the CSOX concentration significantly reduced the initial burst release by 40% for 0.5% CSOX and 78% for 1% CSOX. The release time (T50) was extended from 29 h for the system with HAOX-only to 88 h for HAOX-CSOX. Additionally, the FITC-SPIF released from the DDS increased TGF-β secretion in THP-1 macrophages, with effects comparable to those of FITC-SPIF alone, suggesting that DDS formation may not alter the biological activity of the loaded drug.

Note:
Funding declaration: This work was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813263. This publication has emanated from research supported partly by a grant from the Research Ireland and is co-funded under the European Regional Development Fund under Grant number 13/RC/2073_P2.

Conflict of Interests: Vladimír Velebný has a financial interest in the company Contipro a.s., Dolní Dobrouč, Czech Republic, the commercial producer of hyaluronic acid, Martin Pravda is employee of Contipro a.s.

Keywords: Hydrogel, Synthetic Preimplantation Factor, Hyaluronic Acid, Chondroitin Sulfate, Polyelectrolyte Complexes