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Nanoparticle-mediated local delivery of Methylprednisolone after spinal cord injury.

ABSTRACT: Systemic administration of a high-dose of Methylprednisolone (MP) can reduce neurological deficits after acute spinal cord injury (SCI). However, the use of high-dose MP in treating acute SCI is controversial due to significant dose related side effects and relatively modest improvements in neurological function. Here, using a rat model of SCI, we compare the efficacy of controlled, nanoparticle-enabled local delivery of MP to the injured spinal cord with systemic delivery of MP, and a single local injection of MP without nanoparticles. Based on histological and behavioral data, we report that local, sustained delivery of MP via nanoparticles is significantly more effective than systemic delivery. Relative to systemic delivery, MP-nanoparticle therapy significantly reduced lesion volume and improved behavioral outcomes. Nanoparticle-enabled delivery of MP presents an effective method for introducing MP locally after SCI and significantly enhances therapeutic effectiveness compared to bare MP administered either systemically or locally.

SUBMITTER: Kim YT

PROVIDER: S-EPMC2678685 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Nanoparticle-mediated local delivery of Methylprednisolone after spinal cord injury.

Kim Young-tae YT Caldwell Jon-Michael JM Bellamkonda Ravi V RV

Biomaterials 20090130 13

Systemic administration of a high-dose of Methylprednisolone (MP) can reduce neurological deficits after acute spinal cord injury (SCI). However, the use of high-dose MP in treating acute SCI is controversial due to significant dose related side effects and relatively modest improvements in neurological function. Here, using a rat model of SCI, we compare the efficacy of controlled, nanoparticle-enabled local delivery of MP to the injured spinal cord with systemic delivery of MP, and a single lo ...[more]

PMID: 19185913

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Project description:Drug delivery requires precision in timing, location, and dosage to achieve therapeutic benefits. Challenges in addressing all three of these critical criteria result in poor temporal dexterity, widespread accumulation and off-target effects, and high doses with the potential for toxicity. To address these challenges, we have developed the BiomatErial Accumulating Carriers for On-demand Nanotherapy (BEACON) platform that utilizes an implantable biomaterial to serve as a target for systemically delivered nanoparticles (NPs). With the BEACON system, administered NPs are conjugated with a ligand that has high affinity for a receptor in the implanted biomaterial. To test BEACON, an in vivo spinal cord injury (SCI) model was used as it provides an injury model where the three identified criteria can be tested as it is a dynamic and complicated injury model with no currently approved therapies. Through our work, we have demonstrated temporal dexterity in NP administration by injecting 6 days post-SCI, decreased off-target accumulation with a significant drop in liver accumulation, and retention of our NPs in the target biomaterial. The BEACON system can be applied broadly, beyond the nervous system, to improve systemically delivered NP accumulation at an implanted biomaterial target. STATEMENT OF SIGNIFICANCE: Targeted drug delivery approaches have the potential to improve therapeutic regimens for patients on a case-by-case basis. Improved localization of a therapeutic to site of interest can result in increased efficacy and limit the need for repeat dosing. Unfortunately, targeted strategies can fall short when receptors on cells or tissues are too widespread or change over the course of disease or injury progression. The BEACON system developed herein eliminates the need to target a cell or tissue receptor by targeting an implantable biomaterial with location-controllable accumulation and sustained presentation over time. The targeting paradigm presented by BEACON is widely applicable throughout tissue engineering and regenerative medicine without the need to retool for each new application.

Dataset Information

Nanoparticle-mediated local delivery of Methylprednisolone after spinal cord injury.

Publications

Nanoparticle-mediated local delivery of Methylprednisolone after spinal cord injury.

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