Abstract
To improve the therapeutic efficacy of spinal cord injury (SCI), the methylprednisolone was incorporated into nanoparticles based on the ibuprofen modified dextran. The ibuprofen modified dextran was synthesized using a direct esterification linkage between the carboxylic acids of hydrophobic drug and the hydroxyl groups of the polymer backbone. The morphology of methylprednisolone loaded nanoparticles was evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The therapeutic efficacy of the prepared nanoparticles on the acute SCI model rats was assessed. It is demonstrated that methylprednisolone loaded ibuprofen modified dextran based nanoparticles (MP-loaded NPs) could promote the recovery of neurological deficits, enhance growth of neurons, decrease degeneration of injuried neurons and reduce the tissue tumor necrosis factor alpha (TNF-α) levels significantly in the SCI rats. Subsequently, the study indicates that synthesis of methylprednisolone loaded ibuprofen modified dextran based nanoparticles has a great potential in the synergetic effect treatment for spinal cord injury and nanoparticles based drug delivery system will become a powerful weapon of human conquest of disease.
Highlights
Spinal cord injury (SCI) has become one of the worldwide clinical problems, which can negatively affect both the patients and the health care system [1]
There was a significant improvement in tarlov scores in free MP and MP-loaded NPs group compared to saline and blank NPs group (p < 0.05), at the same time, tarlov scores of MP-loaded NPs group were significantly higher than that in free MP group (d,D3,D5,D7 p < 0.05). These results indicated that free MP and MP-loaded NPs could promote the recovery of neurological deficits of spinal cord injury, while the recovery of nerve function in MP-loaded NPs group was significantly higher than that in free MP group
On account of its nontoxicity, biodegradability, and hydrophilicity, it is a good candidate for biodegradable drug carriers, which would be a significant progress to prepare the copolymers of drug delivery system, and the copolymer based drug delivery system may combine both of their advantages [21, 22]
Summary
Spinal cord injury (SCI) has become one of the worldwide clinical problems, which can negatively affect both the patients and the health care system [1]. Traumatic SCI initiates a cascade of cellular and biochemical events, which lead to devastating sensory and motor functional impairment, neurological deficits, and permanent paralysis, involving disruption of tissue integrity, blood vessel and axon injuries, edema and cell membrane damage [2]. Primary injury is the neurological damage at the time of insult. Secondary damage happens with biochemical changes which cause free radical damage as well as the additional deterioration of the original area caused by lipid peroxidation [3]. The most important mechanisms that cause neuronal damage after SCI are inflammation, lipid peroxidation and oxidative stress [4]. The pathophysiologic and biochemical www.impactjournals.com/oncotarget changes after SCI have been investigated to develop the treatments which may minimize function loss [3]
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