Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

Li, JingLun; Deng, Jiaojiao; Yuan, JinXian; Fu, Jie; Li, Xiaoling; Tong, Aiping; Wang, YueLong; Chen, YangMei; Guo, Gang

doi:10.2147/ijn.s128705

Cited by 24 publications

(10 citation statements)

References 48 publications

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“…ZNS treatment decreased motor dysfunction and denervation muscle atrophy [32,33]. In addition, the ZNS-loaded micelles promoted motor function recovery and enhanced neuron and axon densities in a rat spinal cord injury model [34].…”

Section: Discussionmentioning

confidence: 89%

“…Besides animal PD models, the therapeutic potential of ZNS has been reported in various models of neurological diseases or neuronal injury [31][32][33][34]. ZNS protected spinal motor neurons in wobbler mouse motor neuron disease [32] and mouse embryo primary culture [33].…”

Section: Discussionmentioning

confidence: 99%

“…8-hydroxy-20-deoxyguanosine (8-OHdG) is a biomarker for oxidative stress, and urinary 8-OHdG levels were decreased in ZNS-treated PD patients [38]. These previous studies revealed that ZNS is a multifunctional and neuroprotective drug for several kinds of neuronal diseases [15][16][17][18][23][24][25][26][27][30][31][32][33][34][35][36][37][38].…”

Section: Discussionmentioning

confidence: 99%

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Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study

Ikeda

Yanagihashi

Muramatsu

et al. 2018

Journal of the Neurological Sciences

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This study examined whether zonisamide (ZNS) cotreatment delays dopamine transporter (DAT) reduction on SPECT in Parkinson disease (PD) patients. The study participants met the following criteria: (i) age ≥ 40 years; (ii) HY stage = 2 or 3; (iii) average specific binding ratio (SBR) ≥2.00; (iv) levodopa administration without a prior history of ZNS use before the first DAT-SPECT (baseline). Attending physicians initially determined whether ZNS (25 mg/day) should be used or not. Levodopa and other anti-PD medications were not restricted. The second DAT-SPECT (endpoint) was conducted 1.2 ± 0.2 years after the first DAT-SPECT. Clinicoradiological changes of HY stage, UPDRS parts II to IV, dyskinesia subscore, and SBR were calculated. Statistical differences were analyzed by Student's t-test, ANOVA, or multilogistic analysis. ZNS cotreatment improved wearing off and prevented the development of dyskinesia without additional administration of selegiline, entacapone, and dopamine receptor agonists. The endpoint SBR reduced significantly in the non-ZNS group compared to the baseline (P < .01). The SBR decline rate reduced significantly in the ZNS group (P < .01). ZNS was an independent preventive factor for SBR reduction. These results suggested a beneficial potential that ZNS preserves striatal presynaptic DAT expression and slows disease progression in early-stage PD.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study

Ikeda

Yanagihashi

Muramatsu

et al. 2018

Journal of the Neurological Sciences

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“…Therefore, curtailing this inflammation by modulating activated immunocytes (macrophages, astrocytes, etc.) has been suggested as a promising strategy [ 3 , 4 ]; however, treatment of inflammation after SCI is limited [ 5 ]. Currently, methylprednisolone (MP) is most commonly used in SCI therapy [ 6 ], but MP has shown side effects, including increased risk of general and respiratory infections and hyperglycemia [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of a Silica-Based Drug Delivery System for Spinal Cord Injury Therapy

et al. 2019

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Acute inflammation is a central component in the progression of spinal cord injury (SCI). Anti-inflammatory drugs used in the clinic are often administered systemically at high doses, which can paradoxically increase inflammation and result in drug toxicity. A cluster-like mesoporous silica/arctigenin/CAQK composite (MSN-FC@ARC-G) drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord. In this nanosystem, mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites. The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood–brain barrier. Arctigenin, a Chinese herbal medicine, was loaded into the nanosystem to reduce inflammation. The in vivo results showed that MSN-FC@ARC-G could attenuate inflammation at the injury site. Behavior and morphology experiments suggested that MSN-FC@ARC-G could diminish local microenvironment damage, especially reducing the expression of interleukin-17 (IL-17) and IL-17-related inflammatory factors, inhibiting the activation of astrocytes, thus protecting neurons and accelerating the recovery of SCI. Our study demonstrated that this novel, silica-based drug delivery system has promising potential for clinical application in SCI therapy.

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“…When used in an in vivo rat SCI model, animals treated with the nanomicelles showed improved BBB scores. 100 PEG-DSPE micelles formulated with apamin, a small 18-amino-acid peptide known to penetrate the BBB, was used to target micelles to the spinal cord. 101 Delivery of the micelles that carried curcumin, known to possess antioxidant properties, significantly improved the BBB score of the animals.…”

Section: Introductionmentioning

confidence: 99%

Polyethylene glycol in spinal cord injury repair: a critical review

Lu¹,

Perera²,

Aria³

et al. 2018

JEP

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Polyethylene glycol (PEG) is a synthetic biocompatible polymer with many useful properties for developing therapeutics to treat spinal cord injury. Direct application of PEG as a fusogen to the injury site can repair cell membranes, mitigate oxidative stress, and promote axonal regeneration to restore motor function. PEG can be covalently or noncovalently conjugated to proteins, peptides, and nanoparticles to limit their clearance by the reticuloendothelial system, reduce their immunogenicity, and facilitate crossing the blood–brain barrier. Cross-linking PEG produces hydrogels that can act as delivery vehicles for bioactive molecules including growth factors and cells such as bone marrow stromal cells, which can modulate the inflammatory response and support neural tissue regeneration. PEG hydrogels can be cross-linked in vitro or delivered as an injectable formulation that can gel in situ at the site of injury. Chemical and mechanical properties of PEG hydrogels are tunable and must be optimized for creating the most favorable delivery environment. Peptides mimicking extracellular matrix protein such as laminin and n-cadherin can be incorporated into PEG hydrogels to promote neural differentiation and axonal extensions. Different hydrogel cross-linking densities and stiffness will also affect the differentiation process. PEG hydrogels with a gradient of peptide concentrations or Young’s modulus have been developed to systematically study these factors. This review will describe these and other recent advancements of PEG in the field of spinal cord injury in greater detail.

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Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

Cited by 24 publications

References 48 publications

Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study

Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study

Synthesis and Characterization of a Silica-Based Drug Delivery System for Spinal Cord Injury Therapy

Polyethylene glycol in spinal cord injury repair: a critical review

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