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Polymeric particle-based therapies for acute inflammatory diseases.

ABSTRACT: Acute inflammation is essential for initiating and coordinating the body's response to injuries and infections. However, in acute inflammatory diseases, inflammation is not resolved but propagates further, which can ultimately lead to tissue damage such as in sepsis, acute respiratory distress syndrome and deep vein thrombosis. Currently, clinical protocols are limited to systemic steroidal treatments, fluids and antibiotics that focus on eradicating inflammation rather than modulating it. Strategies based on stem cell therapeutics and selective blocking of inflammatory molecules, despite showing great promise, still lack the scalability and specificity required to treat acute inflammation. By contrast, polymeric particle systems benefit from uniform manufacturing at large scales while preserving biocompatibility and versatility, thus providing an ideal platform for immune modulation. Here, we outline design aspects of polymeric particles including material, size, shape, deformability and surface modifications, providing a strategy for optimizing the targeting of acute inflammation.

SUBMITTER: Brannon ER

PROVIDER: S-EPMC9295115 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Polymeric particle-based therapies for acute inflammatory diseases.

Brannon Emma R ER Guevara M Valentina MV Pacifici Noah J NJ Lee Jonathan K JK Lewis Jamal S JS Eniola-Adefeso Omolola O

Nature reviews. Materials 20220719 10

Acute inflammation is essential for initiating and coordinating the body's response to injuries and infections. However, in acute inflammatory diseases, inflammation is not resolved but propagates further, which can ultimately lead to tissue damage such as in sepsis, acute respiratory distress syndrome and deep vein thrombosis. Currently, clinical protocols are limited to systemic steroidal treatments, fluids and antibiotics that focus on eradicating inflammation rather than modulating it. Strat ...[more]

PMID: 35874960

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Project description:BackgroundLimited data exist regarding the disease course of coronavirus disease 2019 (COVID-19) and its relationship with immunosuppressants among patients with immune-mediated inflammatory diseases (IMIDs). Therefore, this study aims to investigate the association between COVID-19, frequent rheumatological, dermatological, gastrointestinal, and neurological IMIDs and immunosuppressants.MethodsWe conducted a Danish population-based cohort study including all residents living within Capital Region of Denmark and Region Zealand from January 28th, 2020 until September 15th, 2020 with the only eligibility criterion being a test for SARS-CoV-2 via reverse transcription-polymerase chain-reaction. Main outcomes included development of COVID-19, COVID-19-related hospitalization and mortality.ResultsCOVID-19 was less common among patients with IMIDs than the background population (n = 328/20,513 (1.60%) and n = 10,792/583,788(1.85%), p < 0.01, respectively). However, those with IMIDs had a significantly higher risk of COVID-19-related hospitalization (31.1% and 18.6%, p < 0.01, respectively) and mortality (9.8% and 4.3%, p < 0.01, respectively), which were associated with patients older than 65 years, and presence of comorbidities. Furthermore, systemic steroids were independently associated with a severe course of COVID-19 (Odds ratio (OR) = 3.56 (95%CI 1.83-7.10), p < 0.01), while biologic therapies were associated with a reduced risk hereof (OR = 0.47 (95%CI 0.22-0.95), p = 0.04). Patients suspending immunosuppressants due to COVID-19 had an increased risk of subsequent hospitalization (OR = 3.59 (95%CI 1.31-10.78), p = 0.02).ConclusionThis study found a lower occurrence, but a more severe disease course, of COVID-19 among patients with IMIDs, which was associated with the use of systemic steroids for IMIDs and suspension of other immunosuppressants. This study emphasizes the importance of weighing risks before suspending immunosuppressants during COVID-19.

Project description:Inherited retinal diseases (IRDs) are a genetically and phenotypically heterogeneous group of genetic eye disorders. There are more than 300 disease entities, and together this group of disorders affects millions of people globally and is a frequent cause of blindness or low-vision certification. However, each type is rare or ultra-rare. Characteristically, the impaired vision in IRDs is due to retinal photoreceptor dysfunction and loss resulting from mutation in a gene that codes for a retinal protein. Historically, IRDs have been considered incurable and individuals living with these blinding conditions could be offered only supportive care. However, the treatment landscape for IRDs is beginning to evolve. Progress is being made, driven by improvements in understanding of genotype-phenotype relationships, through advances in molecular genetic testing and retinal imaging. Alongside this expanding knowledge of IRDs, the current era of precision medicine is fueling a growth in targeted therapies. This has resulted in the first treatment for an IRD being approved. Several other therapies are currently in development in the IRD space, including RNA-based therapies, gene-based therapies (such as augmentation therapy and gene editing), cell therapy, visual prosthetics, and optogenetics. RNA-based therapies are a novel approach within precision medicine that have demonstrated success, particularly in rare diseases. Three antisense oligonucleotides (AONs) are currently in development for the treatment of specific IRD subtypes. These RNA-based therapies bring several key advantages in the setting of IRDs, and the potential to bring meaningful vision benefit to individuals living with inherited blinding disorders. This review will examine the increasing breadth and relevance of RNA-based therapies in clinical medicine, explore the key features that make AONs suitable for treating genetic eye diseases, and provide an overview of the three-leading investigational AONs in clinical trials.

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Polymeric particle-based therapies for acute inflammatory diseases.

Publications

Polymeric particle-based therapies for acute inflammatory diseases.

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