Polysaccharides constitute one of the most important families of biopolymers. Natural polysaccharide-based drug delivery systems are of constant interest to the scientific community due to their unique properties: biocompatibility, non-toxicity, biodegradability, and high availability. These promising biomaterials protect sensitive active agents and provide their controlled release in targeted sites. The application of natural polysaccharides as drug delivery systems is also intensively developed by Polish scientists. The present review focuses on case studies from the last few years authored or co-authored by research centers in Poland. A particular emphasis was placed on the diversity of the formulations in terms of the active substance carried, the drug delivery route, the composition of the material, and its preparation method.

/pdf/recent-reports-on-polysaccharide-based-materials-for-drug-2yzc9rms.pdf

Recent Reports on Polysaccharide-Based Materials for Drug Delivery

Simple Summary Traumatic brain injury (TBI) is a catastrophic event to the health and life of its sufferers, and it also affects their relatives. In addition to the underlying complications of the resulting condition of affected individuals, there are substantial implications for health and social security systems, since the productive capacity of people who suffer the consequences of a TBI is greatly limited. In this sense, it is essential that studies aimed at a better understanding of the physiological changes resulting from a TBI be carried out. Our work aims to review the main factors related to the alteration of injured brain tissue after TBI, such as inflammatory response, excitotoxicity, and oxidative stress. The adequate understanding of the phenomena resulting from TBI can help improve the care, rehabilitation process and quality of life of the affected people in addition to reducing the associated economic impact. Abstract Traumatic brain injury (TBI) is one of the leading causes of long-lasting morbidity and mortality worldwide, being a devastating condition related to the impairment of the nervous system after an external traumatic event resulting in transitory or permanent functional disability, with a significant burden to the healthcare system. Harmful events underlying TBI can be classified into two sequential stages, primary and secondary, which are both associated with breakdown of the tissue homeostasis due to impairment of the blood–brain barrier, osmotic imbalance, inflammatory processes, oxidative stress, excitotoxicity, and apoptotic cell death, ultimately resulting in a loss of tissue functionality. The present study provides an updated review concerning the roles of brain edema, inflammation, excitotoxicity, and oxidative stress on brain changes resulting from a TBI. The proper characterization of the phenomena resulting from TBI can contribute to the improvement of care, rehabilitation and quality of life of the affected people.

Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far?

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber's hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies. 

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

Abstract Many disease pathologies, particularly in the eye, are induced by oxidative stress. In particular, injury to the optic nerve (ON), or optic neuropathy, is one of the most common causes of vision loss. Traumatic optic neuropathy (TON) occurs when the ON is damaged following blunt or penetrating trauma to either the head or eye. Currently, there is no effective treatment for TON, only management options, namely the systematic delivery of corticosteroids and surgical decompression of the optic nerve. Unfortunately, neither option alleviates the generation of reactive oxygen species (ROS) which are responsible for downstream damage to the ON. Additionally, the systemic delivery of corticosteroids can cause fatal off‐target effects in cases with brain involvement. In this study, we developed a tunable injectable hydrogel delivery system for local methylene blue (MB) delivery using an internal method of crosslinking. MB was chosen due to its ROS scavenging ability and neuroprotective properties. Our MB‐loaded polymeric scaffold demonstrated prolonged release of MB as well as in situ gel formation. Additionally, following rheological characterization, these alginate hydrogels demonstrated minimal cytotoxicity to human retinal pigment epithelial cells in vitro and exhibited injection feasibility through small‐gauge needles. Our chosen MB concentrations displayed a high degree of ROS scavenging following release from the alginate hydrogels, suggesting this approach may be successful in reducing ROS levels following ON injury, or could be applied to other ocular injuries.

Tunable alginate hydrogels as injectable drug delivery vehicles for optic neuropathy

Hydrogel-based wound dressings have been developed for rapid wound healing; however, their adhesive properties have not been adequately investigated. Excessive adhesion to the skin causes wound expansion and pain when hydrogels absorb exudates and swell at wound sites. Herein, we develop a low-adhesion and low-swelling hydrogel dressing using alginate, which is non-adhesive to cells and skin tissue, CaCO3, and carbonated water. The alginate/CaCO3 solution rapidly forms a hydrogel upon the addition of carbonated water, and the CO2 in the hydrogel diffuses into the atmosphere, preventing acidification and obtaining a pH value suitable for wound healing. Remarkably, the skin adhesion and swelling of the hydrogels were 11.9- to 16.5-fold and 1.9-fold lower, respectively, than those of clinical low-adhesion hydrogel dressings. In vivo wound-healing tests in mice demonstrated their therapeutic efficacy, and the prepared hydrogel prevented temporary wound dilation during early healing. These results illustrate the importance of controlling skin adhesion and swelling in wound dressings and demonstrate the potential clinical applications of this wound-friendly hydrogel dressing. 

Low-adhesion and low-swelling hydrogel based on alginate and carbonated water to prevent temporary dilation of wound sites.

The brain and the retina share many physiological similarities, which allows the retina to serve as a model of CNS disease and disorder. In instances of trauma, the eye can even indicate damage to the brain via abnormalities observed such as irregularities in pupillary reflexes in suspected traumatic brain injury (TBI) patients. Elevation of reactive oxygen species (ROS) has been observed in neurodegenerative disorders and in both traumatic optic neuropathy (TON) and in TBI. In a healthy system, ROS play a pivotal role in cellular communication, but in neurodegenerative diseases and post-trauma instances, ROS elevation can exacerbate neurodegeneration in both the brain and the retina. Increased ROS can overwhelm the inherent antioxidant systems which are regulated via mitochondrial processes. The overabundance of ROS can lead to protein, DNA, and other forms of cellular damage which ultimately result in apoptosis. Even though elevated ROS have been observed to be a major cause in the neurodegeneration observed after TON and TBI, many antioxidants therapeutic strategies fail. In order to understand why these therapeutic approaches fail further research into the direct injury cascades must be conducted. Additional therapeutic approaches such as therapeutics capable of anti-inflammatory properties and suppression of other neurodegenerative processes may be needed for the treatment of TON, TBI, and neurodegenerative diseases.

/pdf/oxidative-stress-in-the-brain-and-retina-after-traumatic-23ln49fi.pdf

Oxidative stress in the brain and retina after traumatic injury

Abstract Purpose: Presbyopia—the progressive loss of near focus with age—is primarily a result of changes in lens biomechanics. In particular, the shape of the ocular lens in the absence of zonular tension changes significantly throughout adulthood. Contributors to this change in shape are changes in lens biomechanical properties, continuous volumetric growth lens, and possibly remodeling of the lens capsule. Knowledge in this area is growing rapidly, so the purpose of this mini-review was to summarize and synthesize these gains. Methods: We review the recent literature in this field. Results: The mechanisms governing age-related changes in biomechanical properties remains unknown. We have recently shown that lens growth may be driven by zonular tension. The same mechanobiological mechanism driving lens growth may also lead to remodeling of the capsule, though this remains to be demonstrated. Conclusions: This mini-review focuses on identifying mechanisms which cause these age-related changes, suggesting future work which may elucidate these mechanisms, and briefly discusses ongoing efforts to develop a non-surgical approach for therapeutic management of presbyopia. We also propose a simple model linking lens growth and biomechanical properties.

https://www.tandfonline.com/doi/pdf/10.1080/02713683.2022.2088797?needAccess=true

A Review of Lens Biomechanical Contributions to Presbyopia

The ocular lens is the primary organ within the eye responsible for accommodation. During accommodation, the lens is subject to biomechanical forces. We previously demonstrated that stretching the porcine lens can increase lens epithelial cell proliferation. Although murine lenses are commonly employed in lens research, murine lens stretching has remained unexplored. Murine lens stretching thus represents a novel source of potential discovery in lens research. In the present study, we describe a method for stretching the murine lens by compressing the murine globe embedded in a hydrogel. We hypothesized that, as the eye is compressed along the optic axis, the lens would stretch through zonular tension due to the equatorial region of the eye bulging outward. Our results showed that this led to a compression-dependent increase in murine lens epithelial cell proliferation, suggesting that compression of the embedded murine globe is a viable technique for studying the mechanobiology of the lens epithelium. 

A method for generating zonular tension in the murine eye by embedding and compressing the globe in a hydrogel.


 Optic neuropathy is the loss of visual acuity following damage to the optic nerve (ON). Traumatic optic neuropathy (TON) occurs when the optic nerve is injured following blunt or penetrating trauma to either the head or eye. Current management options for TON include the systemic delivery of corticosteroids and surgical decompression of the optic nerve; however, neither option alleviates the generation of reactive oxygen species (ROS) which are responsible for downstream damage to the ON. Addressing this limitation, an injectable alginate hydrogel system was developed to act as a drug delivery vehicle for methylene blue (MB), a confirmed ROS scavenger and neuroprotective agent. This MB-loaded polymeric scaffold has the ability to be injected as a liquid and rapidly form a gel around the optic nerve following the primary injury, allowing for the prolonged release of MB. The MB-loaded alginate hydrogels demonstrated minimal cytotoxicity to human retinal pigment epithelial (ARPE-19) cells and facilitated gradual MB release over 12 days. Additionally, the MB concentrations displayed a high degree of ROS scavenging after release from the alginate hydrogels, suggesting our approach may be successful in reducing ROS levels following ON injury.

/pdf/alginate-hydrogels-as-injectable-drug-delivery-vehicles-for-4hz24knu3v.pdf

Alginate Hydrogels as Injectable Drug Delivery Vehicles for Optic Neuropathy Treatment

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