An Injectable Click-Crosslinked Hydrogel that Prolongs Dexamethasone Release from Dexamethasone-Loaded Microspheres

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Sustained drug delivery is crucial for effective therapeutic outcomes, reducing dosing frequency and improving patient compliance.
• Injectable hydrogels offer a minimally invasive approach for localized drug delivery, forming depots in situ.
• Hyaluronic acid (HA) is a biocompatible polymer with potential for creating advanced drug delivery matrices.

Purpose of the Study:

• To evaluate the prolonged therapeutic effect of injectable dexamethasone-loaded microspheres (Dex-Ms) formulated with click-crosslinked hyaluronic acid (Cx-HA) hydrogels.
• To compare the in vivo performance of Dex-Ms/Cx-HA with Dex-Ms/Pluronic (PH) and Dex-Ms alone for sustained dexamethasone release.

Main Methods:

• Dexamethasone-loaded microspheres (Dex-Ms) were prepared using ultrasonic atomization.
• Click-crosslinked hyaluronic acid (Cx-HA) was synthesized via click chemistry between TCO-HA and TET-HA.
• Injectable formulations (Dex-Ms/PH and Dex-Ms/Cx-HA) were prepared and tested in Sprague Dawley rats, with drug release monitored in vitro and in vivo.

Main Results:

• The Cx-HA hydrogel demonstrated in vivo persistence for 28 days, significantly longer than the PH hydrogel (6 days).
• Dex-Ms/Cx-HA exhibited significantly slower initial drug release, followed by sustained dexamethasone release over 28 days.
• The Cx-HA hydrogel acted as an external matrix, retarding Dex release from the microspheres, creating an effective drug depot.

Conclusions:

• Injectable Dex-Ms encapsulated within a Cx-HA hydrogel create a minimally invasive drug depot for extended in vivo dexamethasone delivery.
• The Dex-Ms/Cx-HA formulation significantly prolongs therapeutic dexamethasone levels compared to control formulations.
• This injectable click-crosslinked HA hydrogel system shows excellent potential for sustained drug delivery applications.