Abstract
In the injured spinal cord, chondroitin sulfate proteoglycans (CSPGs) are the principal responsible of axon growth inhibition and they contribute to regenerative failure, promoting glial scar formation. Chondroitinase ABC (chABC) is known for being able to digest proteoglycans, thus degrading glial scar and favoring axonal regrowth. However, its classic administration is invasive, infection-prone and clinically problematic. An agarose-carbomer (AC1) hydrogel, already used in SCI repair strategies, was here investigated as a delivery system capable of an effective chABC administration: the material ability to include chABC within its pores and the possibility to be injected into the target tissue were firstly proved. Subsequently, release kinetic and the maintenance of enzymatic activity were positively assessed: AC1 hydrogel was thus confirmed to be a feasible tool for chABC delivery and a promising device for spinal cord injury topic repair strategies.
Highlights
The well known consequences of traumatic spinal cord injury (SCI), e.g., dramatically reduced quality of life in patients and burdensome impact on the public economy, make of it one of the most challenging neurological conditions to investigate [1,2,3]
25 L Chondroitinase ABC (chABC) (Seikagaku Biobusiness Corp., Tokyo, Japan), with a concentration of 2 U/0.5 mL in PBS, was mixed with 25 L of hydrogel, once gel had already been irradiated and cooled down to 37 °C. chABC remained homogeneously entrapped in the pores of the hydrogel at the end of gelation process, to what happened inside Texas-Red dextran (Tx)-loaded hydrogels
The investigated hydrogel is a chemical gel synthesized through a statistical block polycondensation between Carbomer 974P (Figure 1A) and agarose (Figure 1B) [15,16]
Summary
The well known consequences of traumatic spinal cord injury (SCI), e.g., dramatically reduced quality of life in patients and burdensome impact on the public economy, make of it one of the most challenging neurological conditions to investigate [1,2,3]. ChABC delivery is severely limited due to its deactivation and biodistribution, as classical intrathecal deliveries require repeated administrations and are exposed to recurrent infections [5,7] These drawbacks can be overcome by using smart drug delivery systems, providing local sustained release able to both reduce systemic side effects of drugs and increase treatment efficacy [10,11]. Among these systems, hydrogels seem to be very suitable for SCI therapies due to their characteristic properties: (I) the ability to retain water, mimicking living tissues; (II) high biocompatibility; III) the possibility to allow precisely controlled release rates [12,13]. A key quality for a delivery system is to be neutral, i.e., being capable of maintaining the activity of the carried substance: chABC activity was here assessed through its efficacy of digesting decorin, a small proteoglycan [7]
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