A non-invasive nanoparticle-based sustained dual-drug delivery system as an eyedrop for endophthalmitis

Mahaling, Binapani; Baruah, Namrata; Ahamad, Nadim; Maisha, Nuzhat; Lavik, Erin B.; Katti, Dhirendra S.

doi:10.1016/j.ijpharm.2021.120900

Cited by 14 publications

(16 citation statements)

References 51 publications

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“…Oxidative stress causes gliosis in the retina, which is believed to be an attempt by the Müller glia to maintain retinal homeostasis, involving morphological and functional changes. , The change in morphology and increase in GFAP expression are well evident in our results under oxidative stress corroborating with the previous reports. , Although the mechanism of changes in morphology is unknown, there might be an increase in cell adhesion molecules and remodeling of cytoskeletal protein. , Müller glia respond against oxidative stress and protect the photoreceptors and neuronal cells by secreting neurotrophic factors and antioxidants. , The chronic gliosis not only increases GFAP expression, which leads to neuronal cell death with an increase in stiffness, but also increases vascular breakdown . However, oxidative stress itself is detrimental for the glia, leading to an increase in cell death. ,, The glial dysfunction or death indirectly causes neuronal and vascular injury with loss of supportive functions.…”

Section: Discussionsupporting

confidence: 90%

Azithromycin Protects Retinal Glia Against Oxidative Stress-Induced Morphological Changes, Inflammation, and Cell Death

Mahaling

Pandala

Wang

et al. 2022

ACS Bio Med Chem Au

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The reactivity of retinal glia in response to oxidative stress has a significant effect on retinal pathobiology. The reactive glia change their morphology and secret cytokines and neurotoxic factors in response to oxidative stress associated with retinal neurovascular degeneration. Therefore, pharmacological intervention to protect glial health against oxidative stress is crucial for maintaining homeostasis and the normal function of the retina. In this study, we explored the effect of azithromycin, a macrolide antibiotic with antioxidant, immunomodulatory, anti-inflammatory, and neuroprotective properties against oxidative stress-induced morphological changes, inflammation, and cell death in retinal microglia and Müller glia. Oxidative stress was induced by H2O2, and the intracellular oxidative stress was measured by DCFDA and DHE staining. The change in morphological characteristics such as the surface area, perimeter, and circularity was calculated using ImageJ software. Inflammation was measured by enzyme-linked immunosorbent assays for TNF-α, IL-1β, and IL-6. Reactive gliosis was characterized by anti-GFAP immunostaining. Cell death was measured by MTT assay, acridine orange/propidium iodide, and trypan blue staining. Pretreatment of azithromycin inhibits H2O2-induced oxidative stress in microglial (BV-2) and Müller glial (MIO-M1) cells. We observed that azithromycin inhibits oxidative stress-induced morphological changes, including the cell surface area, circularity, and perimeter in BV-2 and MIO-M1 cells. It also inhibits inflammation and cell death in both the glial cells. Azithromycin could be used as a pharmacological intervention on maintaining retinal glial health during oxidative stress.

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Section: Discussionsupporting

confidence: 90%

Azithromycin Protects Retinal Glia Against Oxidative Stress-Induced Morphological Changes, Inflammation, and Cell Death

Mahaling

Pandala

Wang

et al. 2022

ACS Bio Med Chem Au

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“…Endophthalmitis is a devastating and potentially blinding disorder caused by an infection from exogenous or endogenous microorganisms, typically in the vitreous cavity of the eye [ 16 ]. The inflammatory component in endophthalmitis is strongly associated with the recognition of microorganism PAMPs and damaged or dying cell DAMPs by TLRs located on the cell membrane and within endosomes [ 17 , 18 ].…”

Section: Damps In Retinal Disordersmentioning

confidence: 99%

Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders

Mahaling

Low

Beck

et al. 2022

IJMS

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Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from the extracellular and intracellular space of damaged tissue or dead cells. Recent evidence indicates that DAMPs are associated with the sterile inflammation caused by aging, increased ocular pressure, high glucose, oxidative stress, ischemia, mechanical trauma, stress, or environmental conditions, in retinal diseases. DAMPs activate the innate immune system, suggesting their role to be protective, but may promote pathological inflammation and angiogenesis in response to the chronic insult or injury. DAMPs are recognized by specialized innate immune receptors, such as receptors for advanced glycation end products (RAGE), toll-like receptors (TLRs) and the NOD-like receptor family (NLRs), and purine receptor 7 (P2X7), in systemic diseases. However, studies describing the role of DAMPs in retinal disorders are meager. Here, we extensively reviewed the role of DAMPs in retinal disorders, including endophthalmitis, uveitis, glaucoma, ocular cancer, ischemic retinopathies, diabetic retinopathy, age-related macular degeneration, rhegmatogenous retinal detachment, proliferative vitreoretinopathy, and inherited retinal disorders. Finally, we discussed DAMPs as biomarkers, therapeutic targets, and therapeutic agents for retinal disorders.

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“…Based on this property, Binapani Mahaling et al designed PLA core and CHI shell NPs to load azithromycin (AZM) and TA due to the hydrophilicity and mucosal adhesion of CHI. The results showed that the administration system played a good anti-inflammatory role in a mouse microglial cell line (BV-2) and significantly downregulated IL-1β [45].…”

Section: Establishing a Targeting Systemmentioning

confidence: 99%

“…Another pathway by which NPs regulate inflammation is directly inhibiting the proinflammatory componentinduced activation of immune cells and inducing the differentiation of immune cells from immune-killing to immune-protective subtypes. Here, immune cells can be divided into inflammatory cells (such as T cells) involved in specific and nonspecific immunity and other cells associated with inflammation (such as microglia) [22,45,49,50,55]. As Sun K et al proved, TAC-SLNs successfully inhibited the process of the conversion of Th1 cells to Th2 cells and the activation of Th2 cells [10].…”

Section: Modulating Immune Cell Activation and Differentiationmentioning

confidence: 99%

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Immune modulating nanoparticles for the treatment of ocular diseases

Fang

Liu

et al. 2022

J Nanobiotechnol

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Ocular diseases are increasingly influencing people’s quality of life. Complicated inflammatory mechanisms involved in the pathogenic process of ocular diseases make inflammation-targeting treatment a potential therapeutic approach. The limited efficacy of conventional anti-inflammatory therapeutic strategies, caused by various objective factors, such as complex ocular biological barriers, and subjective factors, such as poor compliance, are promoting the development of new therapeutic methods. With the advantages of considerable tissue permeability, a controllable drug release rate, and selective tissue targeting ability, nanoparticles have successfully captured researchers’ attention and have become a research hotspot in treating ocular diseases. This review will focus on the advantages of nanosystems over traditional therapy, the anti-inflammation mechanisms of nanoparticles, and the anti-inflammatory applications of nanoparticles in different ocular diseases (ocular surface diseases, vitreoretinopathy, uveal diseases, glaucoma, and visual pathway diseases). Furthermore, by analyzing the current situation of nanotherapy and the challenges encountered, we hope to inspire new ideas and incentives for designing nanoparticles more consistent with human physiological characteristics to make progress based on conventional treatments. Overall, some progress has been made in nanoparticles for the treatment of ocular diseases, and nanoparticles have rather broad future clinical translation prospects.

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A non-invasive nanoparticle-based sustained dual-drug delivery system as an eyedrop for endophthalmitis

Cited by 14 publications

References 51 publications

Azithromycin Protects Retinal Glia Against Oxidative Stress-Induced Morphological Changes, Inflammation, and Cell Death

Azithromycin Protects Retinal Glia Against Oxidative Stress-Induced Morphological Changes, Inflammation, and Cell Death

Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders

Immune modulating nanoparticles for the treatment of ocular diseases

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