Efficacy Of Local Injecting Methylprednisolone-CGP-hydrogel On Improving Functional Recovery Of Facial Nerve Following Crush Injury

Background:Traumatic facial injury is a common etiology of peripheral paralysis. In clinical practice, glucocorticoids are widely used to treat injuries of the nervous system due to the anti-inflammatory efficacy. Usually, in order to achieve an effective pharmacological effect, high-dose of Gs was administrated after acute injures of nerve system. But, this conventional administration has been shown to increase the likelihood of systemic toxicities and adverse reactions. So how do we use Gs not only enhance neurites regeneration but also reduce or avoid the adverse reaction? Chitosan is a biocompatible and biodegradable cationic polymer, and is widely used in biomedical and pharmaceutical formulations. The CGP-hydrogel can be used as an ideal injectable in situ gelling thermosensitive formulation. What’s more, it has the ability to release therapeutic drugs in a sustained and controlled maner.Objectives:Our goal is to use a novel drug delivery system, CGP-hydrogel, as a drug delivery vehicle to improve clinical outcomes of methylprednisolone (MP) compared to traditional route following facial nerve crush injury.Methods:After the left facial nerves were crushed, adult male Wistar rats were grouped randomly into the following five groups:CGP-MP group, the group receiving20mg/kg MP delivered by CGP-hydrogel at the site of operation; IP-MP group, the group intraperitoneal injection4mg/kg MP successively for five days; CGP-hydrogel group, the group receiving blank CGP-hydrogel at the site of operation; single injury group, the group without any treatment; GF-MP group, the group receiving20mg/kg MP delivered by gelfoam at the site of operation. For each group n=12. As for comparison, six normal rats were also used in this experiment (normal group). After four weeks, the recovery of the eyeblink reflex and vibrissae movement and orientation of the damaged facial nerves was obtained to assess the functional recovery of the paralysis facial. Besides, the change of GAP-43protein expression in the facial nucleus was also monitored. At the same time, morphological changes of injured facial nerves were also observed following injury.Results:Local injecting MP delivered by CGP-hydrogel effectively accelerated the time of facial functional recovery compared to the other four groups. Also, intraperitoneal injection MP enhanced the recovery of some functional parameters compared to single injury group. Local injecting MP delivered by gelfoam can not accelerat the time of facial functional recovery compared to the single injury group. For administrating CGP-hydrogel alone, none effect were observed on the recovery of facial function compared to single injury group. Using CGP-hydrogel to deliver MP could upregulate the expression of GAP-43protein for four weeks while intraperitoneal injection MP could only upregulate for two weeks. On the fourth week following injury, the recovery of facial nerves in CGP-MP group was better than the recovery of the other four groups. Four weeks after the injury, it was demonstrated by improved trichrome staining and HE staining that the CGP-MP group obtained best regeneration compared to the other groups.Conclusions:Our findings suggest that local injecting MP delivered by CGP-hydrogel can get a better effect, and will be a new route to treat facial nerve damage.