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Background. The injuries associated with the spinal cord, including trauma, tumor, or disease, may lead irreparable damage leading to limited or loss of mobility, paralysis, and in extreme cases may loss senses. Methylprednisolone (MP) is often used to treat acute spinal cord injuries but suffers with high dose toxicity. The local administration of MP can overcome the neurological deficits associated with its high-dose systemic administration. Method. In the present study, we have designed a targeted delivery system hyaluronic acid- (HA-) coated polyethylenimine- (PEI-) modified poly lactic-co-glycolic acid (PLGA) nanoparticles (HA-MP-PEI-PLGA) for the localized delivery of MP. The PEI-modified PLGA (PEI-PLGA) nanoparticles were prepared and coated electrostatically by HA. The particles were well characterized using DLS and SEM analysis. The efficacy of the particles was compared with unmodified MP-PEI-PLGA nanoparticles in an in vitro and in vivo model. Results. The synthesis of PEI-PLGA was confirmed using FTIR. The HA-MP-PEI-PLGA and MP-PEI-PLGA were of size and , respectively. The major difference was observed in zeta potential of the nanoparticles where the charge reversal was observed, which was +22.6 mV and -12.9 mV, respectively, for MP-PEI-PLGA and HA-MP-PEI-PLGA. The percentage encapsulation efficiencies (EE) were calculated to be and . The synthesized nanoparticles showed the sustained release of MP which significantly reduced the proinflammatory cytokines and the lesion in HA-MP-PEI-PLGA-treated rats and enhanced the growth of axons and blood vessels; also, it reduced the production of nitric oxide. Conclusion. The results revealed that local administration of HA-MP-PEI-PLGA enhances their efficiency for effective treatment of spinal cord injury (SCI).

Hyaluronic Acid-Coated Nanoparticles for the Localized Delivery of Methylprednisolone to the Injured Spinal Cord