Nanoparticle-Based gene therapy strategies in retinal delivery.

Vision loss and blindness are significant issues in both developed and developing countries. There are a wide variety of aetiologies that can cause vision loss, which are outlined in this review. Although treatment has significantly improved over time for some conditions, nearly half of all people with vision impairment are left untreated.

Computational studies for pre-evaluation of pharmacological profile of gut microbiota-produced gliclazide metabolites.

Background: Gliclazide, a second-generation sulfonylurea derivative still widely used as a second-line treatment for type 2 diabetes mellitus, is well known to be subject to interindividual differences in bioavailability, leading to variations in therapeutic responses among patients. Distinct gut microbiota profiles among individuals are one of the most crucial yet commonly overlooked factors contributing to the variable bioavailability of numerous drugs. In light of the shift towards a more patient-centered approach in diabetes treatment, this study aimed to conduct a pharmacoinformatic analysis of gliclazide metabolites produced by gut microbiota and assess their docking potential with the SUR1 receptor to identify compounds with improved pharmacological profiles compared to the parent drug.

Advanced drug delivery strategies for diabetic retinopathy: current therapeutic advancement, and delivery methods overcoming barriers, and experimental modalities.

Introduction: Diabetic retinopathy, a significant trigger for blindness among working age individuals with diabetes, poses a substantial global health challenge. Understanding its underlying mechanisms is pivotal for developing effective treatments. Current treatment options, such as anti-VEGF agents, corticosteroids, laser photocoagulation, and vitreous surgery, have their limitations, prompting the exploration of innovative approaches like nanocapsules based drug-delivery systems.

Exploring delivery systems for targeted nanotechnology-based gene therapy in the inner ear.

Hearing loss places a significant burden on our aging population. However, there has only been limited progress in developing therapeutic techniques to effectively mediate this condition. This review will outline several of the most commonly utilized practices for the treatment of sensorineural hearing loss before exploring more novel techniques currently being investigated via both and research.

Advances in Extraction, Structure, and Physiochemical Properties of Sorghum Kafirin for Biomaterial Applications: A Review.

Kafirin is an endosperm-specific hydrophobic protein found in sorghum grain and the waste by-product from sorghum biorefineries known as sorghum dried distillers' grain with solubles (DDGS). Because of kafirin's poor nutritional profile (negative nitrogen balance, slow digestibility, and lack of some essential amino acids), its direct human use as a food is restricted. Nevertheless, increased focus on biofuel production from sorghum grain has triggered a new wave of research to use sorghum DDGS kafirin as a food-grade protein for biomaterials with diverse applications.

Polymer-Based Nanoparticles with Probucol and Lithocholic Acid: A Novel Therapeutic Approach for Oxidative Stress-Induced Retinopathies.

Oxidative stress is pivotal in retinal disease progression, causing dysfunction in various retinal components. An effective antioxidant, such as probucol (PB), is vital to counteract oxidative stress and emerges as a potential candidate for treating retinal degeneration. However, the challenges associated with delivering lipophilic drugs such as PB to the posterior segment of the eye, specifically targeting photoreceptor cells, necessitate innovative solutions.

Polymer-Based Nanoparticles for Inner Ear Targeted Trans Differentiation Gene Therapy.

Hearing loss is a significant disability that often goes under recognised, largely due to poor identification, prevention, and treatment. Steps are being made to amend these pitfalls in the investigation of hearing loss, however, the development of a cure to reverse advanced forms remains distant. This review details some current advances in the treatment of hearing loss, with a particular focus on genetic-based nanotechnology and how it may provide a useful avenue for further research.

Probucol-bile acid nanoparticles: a novel approach and promising solution to prevent cellular oxidative stress in sensorineural hearing loss.

The use of antioxidants could thus prove an effective medication to prevent or facilitate recovery from oxidative stress-induced sensorineural hearing loss (SNHL). One promising strategy to prevent SNHL is developing probucol (PB)-based nanoparticles using encapsulation technology and administering them to the inner ear via the established intratympanic route. The preclinical, clinical and epidemiological studies support that PB is a proven antioxidant that could effectively prevent oxidative stress in different study models.

Probucol-Ursodeoxycholic Acid Otic Formulations: Stability and In Vitro Assessments for Hearing Loss Treatment.

Targeted drug delivery is an ongoing aspect of scientific research that is expanding through the design of micro- and nanoparticles. In this paper, we focus on spray dried microparticles as carriers for a repurposed lipophilic antioxidant (probucol). We characterise the microparticles and quantify probucol prior to assessing cytotoxicity on both control and cisplatin treated hair cells (known as House Ear Institute-Organ of Corti 1; HEI-OC1).

Polydimethylsiloxane Organic-Inorganic Composite Drug Reservoir with Gliclazide.

A novel organic-inorganic gliclazide-loaded composite bead was developed by an ionic gelation process using acidified CaCl, chitosan and tetraethylorthosilicate (TEOS) as a crosslinker. The beads were manufactured by crosslinking an inorganic silicone elastomer (-OH terminated polydimethylsiloxane, PDMS) with TEOS at different ratios before grafting onto an organic backbone (Na-alginate) using a 3 factorial experimental design. Gliclazide's encapsulation efficiency (EE%) and drug release over 8 h (% DR 8 h) were set as dependent responses for the optimisation of a pharmaceutical formula (herein referred to as 'G op') by response surface methodology.

Biotechnological Effects of Advanced Smart-Bile Acid Cyclodextrin-Based Nanogels for Ear Delivery and Treatment of Hearing Loss.

Inner ear delivery requires safe and effective drug delivery vehicles incorporating high-viscosity formulations with permeation enhancers. This study designs novel thermoresponsive-smart polymer-bile acid and cyclodextrin-based nanogels for inner ear delivery. Nanogels are examined for their rheological and physical properties.

Synergy between PEDF and Doxorubicin in Breast Cancer Cells: Effects on Metastatic and Metabolic Pathways.

Pigment epithelium-derived factor (PEDF), a serine protease inhibitor (Serpin) family member, shows promise in inhibiting tumour growth. In our study, we explored the effects of PEDF on the efficacy of the frontline chemotherapy agent doxorubicin (Dox) in BC cells. We found that Dox+PEDF treatment significantly reduced glucose uptake in MDA-MB-231 cells compared to the control ( = 0.

Probucol-bile acid based nanoparticles protect auditory cells from oxidative stress: an study.

Excessive free radicals contribute to oxidative stress and mitochondrial dysfunction in sensorineural hearing loss (SNHL). The antioxidant probucol holds promise, but its limited bioavailability and inner ear barriers hinder effective SNHL treatment. We addressed this by developing probucol-loaded nanoparticles with polymers and lithocholic acid and tested them on House Ear Institute-Organ of Corti cells.

The therapeutic potential of probucol and probucol analogues in neurodegenerative diseases.

Neurodegenerative disorders present complex pathologies characterized by various interconnected factors, including the aggregation of misfolded proteins, oxidative stress, neuroinflammation and compromised blood-brain barrier (BBB) integrity. Addressing such multifaceted pathways necessitates the development of multi-target therapeutic strategies. Emerging research indicates that probucol, a historic lipid-lowering medication, offers substantial potential in the realm of neurodegenerative disease prevention and treatment.

Biochemical changes to the inner ear contributing to diabetes-induced hearing loss: possible pharmacological targets for therapy.

Objectives: Biochemical alterations due to diabetes development and progress are complex and diabetes-associated injury to various tissues has been well reported. Nevertheless, a close investigation of the literature demonstrates limited coverage regarding these biochemical and molecular alterations within the inner ear and their impact on the vestibulocochlear environment. A closer look at these may reveal pharmacological targets that could alleviate the severity of disease in patients.

Bile Acid Application in Cell-Targeting for Molecular Receptors in Relation to Hearing: A Comprehensive Review.

Bile acids play important roles in the human body, and changes in their pool can be used as markers for various liver pathologies. In addition to their functional effects in modulating inflammatory responses and cellular survivability, the unconjugated or conjugated, secondary, or primary nature of bile acids accounts for their various ligand effects. The common hydrophilic bile acids have been used successfully as local treatment to resolve drug-induced cell damage or to ameliorate hearing loss.

Novel polysaccharides-bile acid-cyclodextrin gel systems and effects on cellular viability and bioenergetic parameters.

The novel hydrogel systems made from sodium alginate, pectin, beta-cyclodextrin and deoxycholic acid (DCA) were proposed as potential drug-delivery matrices. To ensure biocompatibility, rheological parameters were examined and hydrogels' effects on bioenergetic parameters and cellular viability on murine hepatic, and muscle and pancreatic beta cells. All hydrogels show non-Newtonian, shear thinning behavior.

The effect of deoxycholic acid-based hydrogels on hepatic, muscle and pancreatic beta cells.

The aim of this study is to test the biocompatibility of hydrogels with polysaccharides and bile acids on three murine cell lines. Novel hydrogels containing poloxamer 407, polysaccharides (starch, pectin, acacia, carboxymethyl and methyl 2-hydroxyethyl cellulose) and deoxycholic acid were prepared using cold method, sterilized and used in biological assays to determine effects on hepatic, muscle, and pancreatic beta cells. Hydrogels with deoxycholic acid had tissue-depending effects on cellular survival and bioenergetics, resulting in the best cellular viability and bioenergetics within pancreatic beta cells.

Influence of poly-L-ornithine-bile acid nano hydrogels on cellular bioactivity and potential pharmacological applications.

Cellular bioactivity and pathophysiological changes associated with chronic disorders are considered pivotal detrimental factors when developing novel formulations for biomedical applications. This paper investigates the use of bile acids and synthetic polypeptide poly-L-ornithine (PLO) in formulations and their impacts on a variety of cell lines, with a particular focus on their cellular bioactivity. The hepatic cell line was the most negatively affected by the presence of PLO, while the muscle and beta-pancreatic cell lines did not show as profound of a negative impact of PLO on cellular viability.

Poly-L-lysine as a crosslinker in bile acid and alginate nanoaggregates for gene delivery in auditory cells.

Hearing loss is a condition that may affect a wide array of patients from various backgrounds. There are no cures for sensorineural hearing loss. Gene therapy is one possible method of improving hearing status; however, gene delivery remains challenging.

The biocompatibility and the metabolic impact of thermoresponsive, bile acid-based nanogels on auditory and macrophage cell lines.

Deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are bile acids that may serve as permeation enhancers when incorporated within the nanogel matrix for drug delivery in the inner ear. In this study, thermoresponsive nanogels were formulated with DCA, LCA and UDCA and their rheological properties and biocompatibility were assessed. The impact of nanogel on cellular viability was evaluated via cell viability assay, the impact of nanogels on cellular bioenergetic parameters was estimated by Seahorse mito-stress test and glycolysis-stress test, while the presence of intracellular free radicals was assessed by reactive oxygen species assay.

Pharmaceutical characterization of probucol bile acid-lithocholic acid nanoparticles to prevent chronic hearing related and similar cellular oxidative stress pathologies.

Sensorineural hearing loss has been associated with oxidative stress. However, an antioxidant that passes effectively through the ear remains elusive. Probucol (PB)-based nanoparticles were formed using a spray-drying encapsulation technique, characterized and tested .

The applications of targeted delivery for gene therapies in hearing loss.

Gene therapies are becoming more abundantly researched for use in a multitude of potential treatments, including for hearing loss. Hearing loss is a condition which impacts an increasing number of the population each year, with significant burdens associated. As such, this review will present the concept that delivering a gene effectively to the inner ear may assist in expanding novel treatment options and improving patient outcomes.

Low-dose nano-gel incorporated with bile acids enhanced pharmacology of surgical implants.

Major challenges to islet transplantation in Type 1 diabetes include host-inflammation, which results in failure to maintain survival and functions of transplanted islets. Therefore, this study investigated the applications of encapsulating the bile acid ursodeoxycholic acid (UDCA) with transplanted islets within improved nano-gel systems for Type 1 diabetes treatment. Islets were harvested from healthy mice, encapsulated using UDCA-nano gel and transplanted into the diabetic mice, while the control group was transplanted encapsulated islets without UDCA.