Alkaline-phosphatase triggered self-assemblies enhances the anti-inflammatory property of methylprednisolone in spinal cord injury

Abstract

Methylprednisolone sodium phosphate (MP) is an anti-inflammatory corticosteroid which is used in the treatment of spinal cord injury (SCI), however the overdose of MP has toxic effects Therefore it is prerequisite to develop novel approaches to overcome the side effects of MP and enhance its efficacy. In the present work, we have developed alkaline phosphatase (ALP) trigger self-assembly system of oligopeptides to physically entrap and locally deliver MP. The synthesis of Nap-Phe-Phe-Tyr(H 2 PO 3 )-OH (1P) was achieved using solid phase peptide synthesis and was characterized using mass spectroscopy. The 1P is a hydrogelator, which in presence of ALP self-assembles to form the hydrogel. During the self-assembly of 1P, MP was physically entrapped without losing the physical strength of hydrogel as revealed in the rheology study. The consistency of this hydrogel and the structure was characterized using circular dichroism. The MP was released from the hydrogel in a sustain manner and 80% of the drug release was observed at 120 h. The MP + 1P were non-toxic to the cells at lower concentration however toxicity increases with the increase in concentration of MP. Further, the in-vivo administration of MP + 1P significantly reduces the pro-inflammatory cytokines and the histological analysis revealed improvement in the SCI. In conclusion, it could be stated that the synthesis of 1P for the delivery of MP provides the novel opportunity in for the treatment of SCI.