Aging is considered a contributing factor to many diseases such as cardiovascular disease, Alzheimer’s disease, and hearing loss. Age-related hearing loss, also termed presbycusis, is one of the most common sensory impairments worldwide, affecting one in five people over 50 years of age, and this prevalence is growing annually. Associations have emerged between presbycusis and detrimental health outcomes, including social isolation and mental health. It remains largely untreatable apart from hearing aids, and with no globally established prevention strategies in the clinical setting. Hence, this review aims to explore the pathophysiology of presbycusis and potential therapies, based on a recent advancement in bile acid-based bio-nanotechnologies. A comprehensive online search was carried out using the following keywords: presbycusis, drugs, hearing loss, bile acids, nanotechnology, and more than 150 publications were considered directly relevant. Evidence of the multifaceted oxidative stress and chronic inflammation involvement in cellular damage and apoptosis that is associated with a loss of hair cells, damaged and inflamed stria vascularis, and neuronal signalling loss and apoptosis continues to emerge. New robust and effective therapies require drug delivery deeper into the various layers of the cochlea. Bile acid-based nanotechnology has gained wide interest in its permeation-enhancing ability and potential for numerous applications in treating presbycusis.

Bile acids have recently been studied for potential applications as formulation excipients and enhancers for drug release; however, some bile acids are not suitable for this application. Unconjugated lithocholic acid (ULCA) has recently shown drug formulation-stabilizing and anti-inflammatory effects. Lipophilic drugs have poor gut absorption after an oral dose, which necessitates the administration of high doses and causes subsequent side effects. Probucol (PB) is a highly lipophilic drug with poor oral absorption that resulted in restrictions on its clinical prescribing. Hence, this study aimed to design new delivery systems for PB using ULCA-based matrices and to test drug formulation, release, temperature, and biological effects. ULCA-based matrices were formulated for PB oral delivery by applying the jet-flow microencapsulation technique using sodium alginate as a polymer. ULCA addition to new PB matrices improved the microcapsule’s stability, drug release in vitro (formulation study), and showed a promising effect in ex vivo study (p < 0.05), suggesting that ULCA can optimize the oral delivery of PB and support its potential application in diabetes treatment.

Probucol (PB) is a highly lipophilic drug with potential protective effects on pancreatic β-cells from inflammation and oxidation. PB has poor bioavailability and solubility, and despite many attempts, significant improvement in antidiabetic effects or absorption has yet to be discovered. Recently, the role of bile acids has been established in significant drug formulation stabilisation effects and as cell-penetrating agents. Promising results in pharmaceutical formulation studies on drug stability and release patterns when lithocholic acid (LCA) is conjugated with PB and sodium alginate (SA) have been demonstrated. Thus, this study aimed to develop and characterise PB microcapsules incorporating LCA and examine the biological effects of the microcapsules in vitro and in vivo. PB/LCA microcapsules were prepared using an encapsulation method, ionic gelation vibrational jet flow technology. LCA incorporation in PB microcapsules showed positive effects on β-cells with improved insulin release, antioxidant activity, and PB intracellular uptake. Diabetic mice gavaged LCA-PB microcapsules showed a significant reduction in diabetes signs and symptoms, better survival rate, reduced blood glucose levels, and pro-inflammatory cytokines, with an increase PB level in blood and tissues suggesting a potential therapy for treating diabetes mellitus.

The utilisation of bioartificial organs is of significant interest to many due to their versatility in treating a wide range of disorders. Microencapsulation has a potentially significant role in such organs. In order to utilise microcapsules, accurate characterisation and analysis is required to assess their properties and suitability. Bioartificial organs or transplantable microdevices must also account for immunogenic considerations, which will be discussed in detail. One of the most characterized cases is the investigation into a bioartificial pancreas, including using microencapsulation of islets or other cells, and will be the focus subject of this review. Overall, this review will discuss the traditional and modern technologies which are necessary for the characterisation of properties for transplantable microdevices or organs, summarizing analysis of the microcapsule itself, cells and finally a working organ. Furthermore, immunogenic considerations of such organs are another important aspect which is addressed within this review. The various techniques, methodologies, advantages, and disadvantages will all be discussed. Hence, the purpose of this review is providing an updated examination of all processes for the analysis of a working, biocompatible artificial organ.