Polymers that can change their properties in response to an external or internal stimulus have become an interesting platform for drug delivery systems. Polymeric nanoparticles can be used to decrease the toxicity of drugs, improve the circulation of hydrophobic drugs, and increase a drug’s efficacy. Furthermore, polymers that are sensitive to specific stimuli can be used to achieve controlled release of drugs into specific areas of the body. This review discusses the different stimuli that can be used for controlled drug delivery based on internal and external stimuli. Internal stimuli have been defined as events that evoke changes in different characteristics, inside the body, such as changes in pH, redox potential, and temperature. External stimuli have been defined as the use of an external source such as light and ultrasound to implement such changes. Special attention has been paid to the particular chemical structures that need to be incorporated into polymers to achieve the desired stimuli response. A current trend in this field is the incorporation of several stimuli in a single polymer to achieve higher specificity. Therefore, to access the most recent advances in stimuli-responsive polymers, the focus of this review is to combine several stimuli. The combination of different stimuli is discussed along with the chemical structures that can produce it.
The gastrointestinal (GI) tract is one the biggest mucosal surface in the body and one of the primary targets for the delivery of therapeutics, including immunotherapies. GI diseases, including, e.g., inflammatory bowel disease and intestinal infections such as cholera, pose a significant public health burden and are on the rise. Many of these diseases involve inflammatory processes that can be targeted by immune modulatory therapeutics. However, nonspecific targeting of inflammation systemically can lead to significant side effects. This can be avoided by locally targeting therapeutics to the GI tract and its mucosal immune system. In this review, we discuss nanomaterial-based strategies targeting the GI mucosal immune system, including gut-associated lymphoid tissues, tissue resident immune cells, as well as GI lymph nodes, to modulate GI inflammation and disease outcomes, as well as take advantage of some of the primary mechanisms of GI immunity such as oral tolerance.
The lymph node (LN) is the main site where adaptive immunity is shaped, through education of B and T cells. LNs are highly structured lymphoid organs that compartmentalize B and...
The lymph node (LN) is the main site where adaptive immunity is shaped, through education of B and T
cells. LNs are highly structured lymphoid organs that compartmentalize B and T cells in the outer cortex and inner paracortex, respectively, and are supported by a collagen-rich reticular network. Tissue material properties like viscoelasticity and diffusion of materials within extracellular spaces and their implications on cellular behavior have been a recent hot topic of investigation. Researchers have shown that mechanical properties of LNs are dependent on reticular network and extracellular matrix, and the LN mesh spacing has been estimated at 10 - 20 um. Here, we developed a nanoparticle system to investigate the rheological
properties, including pore size and viscoelasticity, through multiple particle tracking (MPT) combined with LN slice cultures. We first determined that dense coatings with polyethylene glycol (PEG) are necessary to allow nanoparticles to diffuse within the extracellular spaces of the LNs. We demonstrate that despite differences in functionality, extracellular tissue properties and mesh spacing do not change significantly in the cortex and paracortex, where B and T cells are educated, respectively, though nanoparticle diffusion was slightly reduced in B cell zones, indicating a higher viscosity. Our studies also confirm that LNs exhibit viscoelastic properties, with an initial solid-like response followed by stress-relaxation at higher frequencies. Finally, we found that nanoparticle diffusion is dependent on LN location, with nanoparticles in skin draining LNs (sdLNs) exhibiting higher diffusion compared to mesenteric LNs (mLNs). This phenomenon is also reflected in the slightly reduced nanoparticle diffusion coefficient and pore size in mLNs. Our data shed new light onto LN interstitial tissue properties, pore size, and define surface chemistry parameters required for nanoparticles to diffuse within LN interstitium. These studies provide both a tool for studying LNs interstitium and design criteria for nanoparticles targeting LN interstitial spaces, which has recently received increasing attention.
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