Drug delivery to macrophages: A review of targeting drugs and drug carriers to macrophages for inflammatory diseases

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS). The early stage is characterized by relapses and the later stage, by progressive disability. Results from experimental and clinical investigations have demonstrated that microglia and macrophages play a key part in the disease course. These cells actively initiate immune infiltration and the demyelination cascade during the early phase of the disease; however, they promote remyelination and alleviate disease in later stages. This review aims to provide a comprehensive overview of the existing knowledge regarding the neuromodulatory function of macrophages and microglia in the healthy and injured CNS, and it discusses the feasibility of harnessing microglia and macrophage physiology to treat MS. The review encourages further investigations into macrophage-targeted therapy, as well as macrophage-based drug delivery, for realizing efficient treatment strategies for MS.

/pdf/targeting-microglia-and-macrophages-a-potential-treatment-3p7zhwvrad.pdf

Targeting Microglia and Macrophages: A Potential Treatment Strategy for Multiple Sclerosis.

Multiple Sclerosis (MS) is a chronic demyelinating autoimmune disease primarily affecting young adults. Despite an unclear causal factor, symptoms and pathology arise from the infiltration of peripheral immune cells across the blood brain barrier. Accounting for the largest fraction of this infiltrate, macrophages are functionally heterogeneous innate immune cells capable of adopting either a pro or an anti-inflammatory phenotype, a phenomenon dependent upon cytokine milieu in the CNS. This functional plasticity is of key relevance in MS, where the pro-inflammatory state dominates the early stage, instructing demyelination and axonal loss while the later anti-inflammatory state holds a key role in promoting tissue repair and regeneration in later remission. This review highlights a potential therapeutic benefit of modulating macrophage polarisation to harness the anti-inflammatory and reparative state in MS. Here, we outline the role of macrophages in MS and look at the role of current FDA approved therapeutics in macrophage polarisation. Moreover, we explore the potential of particulate carriers as a novel strategy to manipulate polarisation states in macrophages, whilst examining how optimising macrophage uptake via nanoparticle size and functionalisation could offer a novel therapeutic approach for MS.

https://www.mdpi.com/2073-4409/8/6/543/pdf

Nanomodulation of Macrophages in Multiple Sclerosis

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by the infiltration of mononuclear cells into the CNS and a subsequent inflammation of the brain. Monocytes are implicated in disease pathogenesis not only in their function as potential antigen-presenting cells involved in the local reactivation of encephalitogenic T cells but also by independent effector functions contributing to structural damage and disease progression. However, monocytes also have beneficial effects as they can exert anti-inflammatory activity and promote tissue repair. Glucocorticoids (GCs) are widely used to treat acute relapses in MS patients. They act on a variety of cell types but their exact mechanisms of action including their modulation of monocyte function are not fully understood. Here we investigated effects of the therapeutically relevant GC methylprednisolone (MP) on monocytes from healthy individuals and MS patients in vitro and in vivo. The monocyte composition in the blood was different in MS patients compared to healthy individuals, but it was only marginally affected by MP treatment. In contrast, application of MP caused a marked shift toward an anti-inflammatory monocyte phenotype in vitro and in vivo as revealed by an altered gene expression profile. Chemotaxis of monocytes toward CCL2, CCL5, and CX3CL1 was increased in MS patients compared to healthy individuals and further enhanced by MP pulse therapy. Both of these migration-promoting effects were more pronounced in MS patients with an acute relapse than in those with a progressive disease. Interestingly, the pro-migratory GC effect was independent of chemokine receptor levels as exemplified by results obtained for CCR2. Collectively, our findings suggest that GCs polarize monocytes toward an anti-inflammatory phenotype and enhance their migration into the inflamed CNS, endowing them with the capacity to suppress the pathogenic immune response.

/pdf/glucocorticoid-therapy-of-multiple-sclerosis-patients-3x6n1ksn6g.pdf

Glucocorticoid Therapy of Multiple Sclerosis Patients Induces Anti-inflammatory Polarization and Increased Chemotaxis of Monocytes.

Brain is by far the most complex organ in the body. It is involved in the regulation of cognitive, behavioral, and emotional activities. The organ is also a target for many diseases and disorders ranging from injuries to cancers and neurodegenerative diseases. Brain diseases are the main causes of disability and one of the leading causes of deaths. Several drugs that have shown potential in improving brain structure and functioning in animal models face many challenges including the delivery, specificity, and toxicity. For many years, researchers have been facing challenge of developing drugs that can cross the physical (blood-brain barrier), electrical, and chemical barriers of the brain and target the desired region with few adverse events. In recent years, nanotechnology emerged as an important technique for modifying and manipulating different objects at the molecular level to obtain desired features. The technique has proven to be useful in diagnosis as well as treatments of brain diseases and disorders by facilitating the delivery of drugs and improving their efficacy. As the subject is still hot, and new research findings are emerging, it is clear that nanotechnology could upgrade health care systems by providing easy and highly efficient diagnostic and treatment methods. In this review, we will focus on the application of nanotechnology in the diagnosis and treatment of brain diseases and disorders by illuminating the potential of nanoparticles.

/pdf/the-application-of-nanotechnology-for-the-diagnosis-and-2qh6uk78ka.pdf

The Application of Nanotechnology for the Diagnosis and Treatment of Brain Diseases and Disorders.

Targeted delivery of glucocorticoids to macrophages in a mouse model of multiple sclerosis using inorganic-organic hybrid nanoparticles.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Sarah Ring

Author Tools

Chat about Author

Papers

Targeted delivery of glucocorticoids to macrophages in a mouse model of multiple sclerosis using inorganic-organic hybrid nanoparticles.