Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats

Xiao, Rong; Ji, Yinghong; Zhu, Xiangjia; Yang, Jin; Qian, Dong−Jin; Mo, Xiaoliang; Lü, Yi

doi:10.2147/ijn.s184574

Cited by 52 publications

(29 citation statements)

References 25 publications

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“…In addition to the peptides cited above, some evidence exists for an effect of a few other peptides that is both neuroprotective and vasoprotective. Indeed, antioxidative, anti-inflammatory, and/or antiapoptotic actions together with effects preventing VEGF upregulation and/or BRB breakdown have been described for the peptides growth hormone-releasing hormone (Thounaojam et al, 2017), insulin (Rong et al, 2018), melatonin (Djordjevic et al, 2018), substance P (D'alessandro et al, 2014), and vasoinhibins (Garcia et al, 2008; Arredondo Zamarripa et al, 2014).…”

Section: Neuropeptidesmentioning

confidence: 99%

Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

2019

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Diabetic retinopathy (DR) is a common complication of diabetes and constitutes a major cause of vision impairment and blindness in the world. DR has long been described exclusively as a microvascular disease of the eye. However, in recent years, a growing interest has been focused on the contribution of neuroretinal degeneration to the pathogenesis of the disease, and there are observations suggesting that neuronal death in the early phases of DR may favor the development of microvascular abnormalities, followed by the full manifestation of the disease. However, the mediators that are involved in the crosslink between neurodegeneration and vascular changes have not yet been identified. According to our hypothesis, vascular endothelial growth factor (VEGF) could probably be the most important connecting link between the death of retinal neurons and the occurrence of microvascular lesions. Indeed, VEGF is known to play important neuroprotective actions; therefore, in the early phases of DR, it may be released in response to neuronal suffering, and it would act as a double-edged weapon inducing both neuroprotective and vasoactive effects. If this hypothesis is correct, then any retinal stress causing neuronal damage should be accompanied by VEGF upregulation and by vascular changes. Similarly, any compound with neuroprotective properties should also induce VEGF downregulation and amelioration of the vascular lesions. In this review, we searched for a correlation between neurodegeneration and vasculopathy in animal models of retinal diseases, examining the effects of different neuroprotective substances, ranging from nutraceuticals to antioxidants to neuropeptides and others and showing that reducing neuronal suffering also prevents overexpression of VEGF and vascular complications. Taken together, the reviewed evidence highlights the crucial role played by mediators such as VEGF in the relationship between retinal neuronal damage and vascular alterations and suggests that the use of neuroprotective substances could be an efficient strategy to prevent the onset or to retard the development of DR.

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Section: Neuropeptidesmentioning

confidence: 99%

Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

2019

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“…Tunable biodegradability can also be conferred by adding ester or urethane bonds into the polymer backbone to allow for hydrolysis [95]. PEG-based hydrogels have been used to encapsulate both hydrophilic and hydrophobic drugs, including hormones such as insulin [96] and steroids [97].…”

Section: Classifying Hydrogels Based On Polymer Typementioning

confidence: 99%

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Seah

Zhao

Lin

et al. 2020

Eye

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Anti-vascular endothelial growth factors (anti-VEGF) have become the most common treatment modality for many retinal diseases. These include neovascular age-related macular degeneration (n-AMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusions (RVO). However, these drugs are administered via intravitreal injections that are associated with sight-threatening complications. The most feared of these complications is endophthalmitis, a severe infection of the eye with extremely poor visual outcomes. Patients with retinal diseases typically have to undergo multiple injections before achieving the desired therapeutic effect. Each injection incurs the risk of the sight-threatening complications. As such, there has been great interest in developing sustained delivery platforms for anti-VEGF agents to the posterior segment of the eye. In recent years, there have been various strategies that have been conceptualised. These include non-biodegradable implants, nano-formulations and hydrogels. In this review, the barriers of drug delivery to the posterior segment of the eye will be explained. The characteristics of an ideal sustained delivery platform will then be discussed. Finally, the current available strategies will be analysed with the above-mentioned characteristics in mind to determine the advantages and disadvantages of each sustained drug delivery modality. Through the above, this review attempts to provide an overview of the sustained delivery platforms in their various phases of development.These authors contributed equally: Ivan Seah Yu Jun, Zhao Xin Xin 1234567890();,:1234567890();,:

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“…The preparation of materials at room temperature is largely easy just by mixing liquid. Insulin-loaded chitosan nanoparticle/ICNPH (1:20 ratio) reduced retinal cell apoptosis greater compared to insulin alone in an in vivo assay using diabetic retinopathy model rats through a single subconjunctival injection [54]. The insulin delivery system using ICNPH might be also effective to intranasal administration, because appropriate gelatinization on the mucus layer of the epithelium delays mucociliary clearance.…”

Section: Intranasal Administration Using Nanoparticlesmentioning

confidence: 99%

Shortcut Approaches to Substance Delivery into the Brain Based on Intranasal Administration Using Nanodelivery Strategies for Insulin

Tashima

2020

Molecules

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The direct delivery of central nervous system (CNS) drugs into the brain after administration is an ideal concept due to its effectiveness and non-toxicity. However, the blood–brain barrier (BBB) prevents drugs from penetrating the capillary endothelial cells, blocking their entry into the brain. Thus, alternative approaches must be developed. The nasal cavity directly leads from the olfactory epithelium to the brain through the cribriform plate of the skull bone. Nose-to-brain drug delivery could solve the BBB-related repulsion problem. Recently, it has been revealed that insulin improved Alzheimer’s disease (AD)-related dementia. Several ongoing AD clinical trials investigate the use of intranasal insulin delivery. Related to the real trajectory, intranasal labeled-insulins demonstrated distribution into the brain not only along the olfactory nerve but also the trigeminal nerve. Nonetheless, intranasally administered insulin was delivered into the brain. Therefore, insulin conjugates with covalent or non-covalent cargos, such as AD or other CNS drugs, could potentially contribute to a promising strategy to cure CNS-related diseases. In this review, I will introduce the CNS drug delivery approach into the brain using nanodelivery strategies for insulin through transcellular routes based on receptor-mediated transcytosis or through paracellular routes based on escaping the tight junction at the olfactory epithelium.

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Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats

Cited by 52 publications

References 25 publications

Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

Relationships Between Neurodegeneration and Vascular Damage in Diabetic Retinopathy

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

Shortcut Approaches to Substance Delivery into the Brain Based on Intranasal Administration Using Nanodelivery Strategies for Insulin

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