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.

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.

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.

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.

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.

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.

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.

Potentials and limitations of pharmaceutical and pharmacological applications of bile acids in hearing loss treatment.

Hearing loss is a worldwide epidemic, with approximately 1.5 billion people currently struggling with hearing-related conditions. Currently, the most wildly used and effective treatments for hearing loss are primarily focus on the use of hearing aids and cochlear implants.

Novel Nanoencapsulation Technology and its Potential Role in Bile Acid-Based Targeted Gene Delivery to the Inner Ear.

Hearing loss impacts a large proportion of the global population. Damage to the inner ear, in particular the sensitive hair cells, can impact individuals for the rest of their lives. There are very limited options for interventions after damage to these cells has occurred.

Novel hydrogel comprising non-ionic copolymer with various concentrations of pharmacologically active bile acids for cellular injectable gel.

Deoxycholic acid (DCA) is a bile acid capable of forming micelles and modifying the properties of hydrogels. We incorporated DCA in sodium alginate (SA) and poloxamer 407 matrices creating novel DCA-copolymer hydrogel for therapeutic delivery. Hydrogels were assessed for common rheological properties.

Impact of Novel Teflon-DCA Nanogel Matrix on Cellular Bioactivity.

The biocompatibility and effects on cells' bioactivity of developed pharmaceuticals are crucial properties, required to permit their safe delivery. Nanogel matrices offer a promising role in emerging pharmaceutics; however, it is crucial that they and their excipients do not demonstrate detrimental effects on the cells to which they interact. This study investigated the use of Teflon and the secondary bile acid deoxycholic acid in the formation of novel nanogel matrices.

Reduced Cytokine Tumour Necrosis Factor by Pharmacological Intervention in a Preclinical Study.

Recent preclinical studies in our laboratory have shown that the bile acid profile is altered during diabetes development and such alteration has been linked to the diabetes-associated inflammatory profile. Hence, this study aimed to investigate if the first-line antidiabetic drug metformin will alter the bile acid profile and diabetes-associated inflammation in a murine model of pre-type 2 diabetes. C57 mice were randomly allocated into three equal groups of eight.

The Effect of Deoxycholic Acid on Chitosan-Enabled Matrices for Tissue Scaffolding and Injectable Nanogels.

The pathophysiology of a multitude of diseases is influenced by bioenergetic dysfunction. Healthy mitochondria are presented as essential for the regulation and function of multiple cell types, including the cells of relevance for this research: pancreatic beta cells, muscle cells, and liver cells. Hence, effects of hydrogels (particularly nanogels) on bioenergetics needs to be taken into account when designing optimum delivery matrices.

Pharmacological Dose-Effect Profiles of Various Concentrations of Humanised Primary Bile Acid in Encapsulated Cells.

Bile acids (BA)s are known surfactants and well-documented to play a major role in food digestion and absorption. Recently, potential endocrinological and formulation-stabilisation effects of BAs have been explored and their pharmacological effects on supporting cell survival and functions have gained wide interest. Hence, this study aimed to explore the hyper-glycaemic dependent dose-effect of the BA chenodeoxycholic acid (CDCA) when encapsulated with pancreatic β-cells, allowing assessment of CDCA's impacts when encapsulated.

Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions.

Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems.

Single-Cellular Biological Effects of Cholesterol-Catabolic Bile Acid-Based Nano/Micro Capsules as Anti-Inflammatory Cell Protective Systems.

Recent studies in our laboratories have shown promising effects of bile acids in ➀ drug encapsulation for oral targeted delivery (via capsule stabilization) particularly when encapsulated with Eudragit NM30D and ➁ viable-cell encapsulation and delivery (via supporting cell viability and biological activities, postencapsulation). Accordingly, this study aimed to investigate applications of bile acid-Eudragit NM30D capsules in viable-cell encapsulation ready for delivery. Mouse-cloned pancreatic β-cell line was cultured and cells encapsulated using bile acid-Eudragit NM30D capsules, and capsules' images, viability, inflammation, and bioenergetics of encapsulated cells assessed.

Taurine Grafted Micro-Implants Improved Functions without Direct Dependency between Interleukin-6 and the Bile Acid Lithocholic Acid in Plasma.

A recent study showed an association between diabetes development and the bile acid lithocholic acid (LCA), while another study demonstrated positive biological effects of the conjugated bile acid, taurocholic acid (TCA), on pancreatic cells. Thus, this study aimed to encapsulate TCA with primary islets (graft) and study the biological effects of the graft, post-transplantation, in diabetic mice, including effects on LCA concentrations. Sixteen mature adult mice were made diabetic and randomly divided into two equal groups, control and test (transplanted encapsulated islets without or with TCA).