Multiple Sclerosis (MS) is an autoimmune disorder affecting the central nervous system (CNS). Conventional drug delivery methods face challenges in reaching the CNS due to the presence of the blood-brain barrier.[1] This study presents a novel transcranial drug delivery device as a potential solution for MS treatment. The device comprises (1) an Ommaya pod [2] (designed and refined by the PMSMatTrain research consortium) and (2) an injectable hydrogel containing Minocycline (MN) - loaded polyelectrolyte complexes (PEC). MN was suggested as a promising drug for MS therapy since it showed increased oligodendrocyte survival and enhanced remyelination [3], potentially reversing the disease severity In Vivo. However, MN is widely known to be unstable under certain conditions, such as exposure to light, temperature, and alkaline pH. [4] This instability can compromise its therapeutic efficacy.

To address the instability of MN, we developed a hydrogel based on hyaluronic acid polyaldehyde crosslinked by oxime ligation. This hydrogel incorporates PEC, formed through electrostatic attraction involving MN, Calcium Chloride, Gelatine, Chondroitin Sulfate (CS), or aldehyde-modified Chondroitin sulfate (CSOX). CS or CSOX aids the formation of free and immobilised PEC, respectively. This PEC-containing hydrogel should act as a depot, providing the release of the loaded drug. We characterized the influence of the delivery system on the MN release profile by measuring its cumulative drug release and model fitting for the release kinetics. Simultaneously, we conducted rheological measurements to evaluate the gelation kinetics ensuring injectability.

The findings of this study demonstrate the efficacy of this hybrid platform as an effective drug delivery system, evidenced by the stability improvement and prolonged delivery of MN for up to three weeks In Vitro. The versatility of this platform provides immense potential for various clinical therapies and can be easily modified for different biological applications.