Development of an in situ polymeric hydrogel implant of methylprednisolone for spinal injuries

Purpose: To prepare and characterize in situ gel-forming implants of methylprednisolone for the treatment of spinal cord injuries.
Methods: In situ hydrogels of methylprednisolone were prepared by dispersing polylactide glycolic acid (PLGA) polymer and methylprednisolone in N-methyl-pyrrolidone solvent, and subsequent membrane sterilization. Hydrogels were prepared using varying concentrations of PLGA polymer. The physicochemical properties of hydrogels, including visual appearance, clarity, pH, viscosity, drug content, and in vitro drug release, were characterized. In vivo studies were performed to examine anti-inflammatory activity (paw edema test) and in vivo motor function activity in a rat spinal injury model after injecting the hydrogels into rats.
Results: The physicochemical properties of the gels were satisfactory. F1, F2, F3, and F4 formulations showed 99.67, 95.29, 88.89 and 88.20 % drug release, respectively, at the end of 7 days. In vivo anti-inflammatory activity was highest for F1 (62.85 %). Motor function activity scores (arbitrary scale) for the F1, F2, F3 and F4 formulations were 4.82 ± 0.12, 4.70 ± 0.12, 4.68 ± 0.02, and 4.60 ± 0.05, respectively, and were higher (p < 0.05) for F1, F2 and F3) than for the standard (methylprednisolone, 30 mg/kg body weight, iv; activity score, 4.59 ± 0.20).
Conclusions: The in situ hydrogels of methylprednisolone developed may be useful for the effective management of spinal cord injuries in patients. However, further investigations are required to ascertain their suitability for clinical use.

Keywords
Methylprednisolone; In situ hydrogel; Spinal injury; Motor activity; Implant