Superoxide Dismutase‐Loaded Porous Polymersomes as Highly Efficient Antioxidants for Treating Neuropathic Pain

Kartha, Sonia; Yan, Lesan; Weisshaar, Christine L.; Ita, Meagan E.; Shuvaev, Vladimir V.; Muzykantov, Vladimir R.; Tsourkas, Andrew; Winkelstein, Beth A.; Cheng, Zhiliang

doi:10.1002/adhm.201700500

Cited by 42 publications

(46 citation statements)

References 53 publications

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“…However, that reflex outcome does not translate to the human experience of pain because it fails to capture the cortical and affective components involved in the perception of pain 1 – 4 . In many studies, peripheral sensitivity is measured using mechanical stimuli to illicit a withdrawal response, defining a threshold for sensitivity 5 – 10 . Although this method is useful for investigating some forms of sensitivity, it assesses only the evoked component of pain 3 and nociceptive pain pathways 11 .…”

Section: Introductionmentioning

confidence: 99%

Grading facial expression is a sensitive means to detect grimace differences in orofacial pain in a rat model

Sperry

Welch

et al. 2018

Sci Rep

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Although pre-clinical models of pain are useful for defining relationships between biological mechanisms and pain, common methods testing peripheral sensitivity do not translate to the human pain experience. Facial grimace scales evaluate affective pain levels in rodent models by capturing and scoring spontaneous facial expression. But, the Rat Grimace Scale (RGS) has not assessed the common disorder of temporomandibular joint (TMJ) pain. A rat model of TMJ pain induced by jaw loading (1 hr/day for 7 days) was used to investigate the time course of RGS scores and compare them between different loading magnitudes with distinct peripheral sensitivity profiles (0N–no sensitivity, 2N–acute sensitivity, 3.5N–persistent sensitivity). In the 3.5N group, RGS is elevated over baseline during the loading period and one day after loading and is correlated with peripheral sensitivity (ρ = −0.48, p = 0.002). However, RGS is not elevated later when that group exhibits peripheral sensitivity and moderate TMJ condylar cartilage degeneration. Acutely, RGS is elevated in the 3.5N loading group over the other loading groups (p < 0.001). These findings suggest that RGS is an effective tool for detecting spontaneous TMJ pain and that spontaneous pain is detectable in rats that develop persistent TMJ sensitivity, but not in rats with acute resolving sensitivity.

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Section: Introductionmentioning

confidence: 99%

Grading facial expression is a sensitive means to detect grimace differences in orofacial pain in a rat model

Sperry

Welch

et al. 2018

Sci Rep

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“…So far, several nanocarriers have been designed to carry antioxidant molecules and allow for improved pharmacokinetic properties, increased physical stability, protection from interactions with the environment, and enhancement of their bioactivity. [ 202,203 ] For instance, NPs with encapsulated SOD exhibit significant neuroprotective properties under oxidative stress conditions both in vitro and in vivo. [ 204,205 ] In fact, the superior efficacy of SOD‐NPs appears to be attributed to improved stability, protection against degradation/proteolysis, and increased cellular uptake of the enzyme.…”

Section: Nanocarrier‐based Delivery Of Antioxidantsmentioning

confidence: 99%

Redox‐Responsive Nanobiomaterials‐Based Therapeutics for Neurodegenerative Diseases

Eleftheriadou

Kesidou

Moura

et al. 2020

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dementia, which result from chronic and progressive loss of neuronal function. In view of an ageing population, disorders of the brain are likely to establish the principal economic challenge in the future of healthcare. [1] The total cost of dementia to society in the UK alone is £26.3 billion, and this is expected to double over the next 30 years given that prevalence is projected to rise by 40% in the coming decade alone. [2] Among NDs, significant attention has been paid to Alzheimer's disease (AD) and Parkinson's disease (PD) given their severe complications and economic burdens. AD, which accounts for the vast majority of age-related dementia, is a progressive disorder that is characterized by gradual neuronal loss and accumulation of proteins, namely extracellular amyloid-β plaques and intracellular tau tangles. [3] PD is a progressive ND resulting from the loss of specific dopaminergic (DA) neurons in the substantia nigra pars compacta and reduced DA levels in the nigrostriatal DA pathway in the brain. [4,5] Despite significant progress in the management of NDs over the recent years, the early diagnostic and treatment options remain limited. Patients currently suffering from NDs have no available disease-modifying treatments. Instead, patients are offered a therapeutic plan focused on the management of their ND symptoms, whilst concurrently attempting to reduce the adverse effects associated with the medications used. The systemic delivery of drugs to the central nervous system (CNS) is complex due to their poor delivery to the brain, extensive firstpass metabolism which reduces their half-life, and the sideeffects resulting from the drug acting on non-target peripheral tissues. [6] The mainstay of current treatments for NDs is typically through oral administration. For PD medications include L-dopa, carbidopa (peripheral inhibitor of L-dopa into DOPA), dopaminergic agonists, Entacapone (Catechol-O-methyl transferase inhibitor), monoamine oxidase-B inhibitors, amongst others. Other routes of drug administration exist such as subcutaneous injection of dopaminergic agonists. Interestingly, deep brain stimulation has also been offered to those patients resistant to medical therapy but again associated with significant adverse effects. L-Dopa, which is considered the most effective treatment in the short-term for PD, [7] is related to longterm wearing-off phenomena, dyskinesias, and neuropsychiatric disorders. [8] Redox regulation has recently been proposed as a critical intracellular mechanism affecting cell survival, proliferation, and differentiation. Redox homeostasis has also been implicated in a variety of degenerative neurological disorders such as Parkinson's and Alzheimer's disease. In fact, it is hypothesized that markers of oxidative stress precede pathologic lesions in Alzheimer's disease and other neurodegenerative diseases. Several therapeutic approaches have been suggested so far to improve the endogenous defense against oxidative stress and its harmful effects. Among such approaches, the use o...

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“…Another interesting therapeutic application is neuropathic pain treatment with SOD‐loaded porous polymer vesicles, which was developed by Cheng and co‐workers . Neuropathic pain is generally caused by injury to the spinal nerve root.…”

Section: In Vivo Therapeutic Biocatalytic Nanoreactorsmentioning

confidence: 99%

Biotransporting Biocatalytic Reactors toward Therapeutic Nanofactories

Nishimura

Akiyoshi

2018

Advanced Science

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Drug‐delivery systems (DDSs), in which drug encapsulation in nanoparticles enables targeted delivery of therapeutic agents and their release at specific disease sites, are important because they improve drug efficacy and help to decrease side effects. Although significant progress has been made in the development of DDSs for the treatment of a wide range of diseases, new approaches that increase the scope and effectiveness of such systems are still needed. Concepts such as nanoreactors and nanofactories are therefore attracting much attention. Nanoreactors, which basically consist of vesicle‐encapsulated enzymes, provide prodrug conversion to therapeutic agents rather than simple drug delivery. Nanofactories are an extension of this concept and combine the features of nanoreactors and delivery carriers. Here, the required features of nanofactories are discussed and an overview of current strategies for the design and fabrication of different types of nanoreactors, i.e., systems based on lipid or polymer vesicles, capsules, mesoporous silica, viral capsids, and hydrogels, and their respective advantages and shortcomings, is provided. In vivo applications of biocatalytic reactors in the treatment of cancer, glaucoma, neuropathic pain, and alcohol intoxication are also discussed. Finally, the prospects for further progress in this important and promising field are outlined.

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Superoxide Dismutase‐Loaded Porous Polymersomes as Highly Efficient Antioxidants for Treating Neuropathic Pain

Cited by 42 publications

References 53 publications

Grading facial expression is a sensitive means to detect grimace differences in orofacial pain in a rat model

Grading facial expression is a sensitive means to detect grimace differences in orofacial pain in a rat model

Redox‐Responsive Nanobiomaterials‐Based Therapeutics for Neurodegenerative Diseases

Biotransporting Biocatalytic Reactors toward Therapeutic Nanofactories

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