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Aim: 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. Materials & methods: 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. The two groups' survival plot, blood glucose, and inflammation and bile acid profiles were analyzed. Results & conclusion: UDCA-nano gel enhanced survival, glycemia and normalized bile acids' profile, which suggests improved islets functions and potential adjunct treatment for insulin therapy.

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. However, these have many limitations, highlighting the importance of developing a pharmacological solution that may be used to overcome barriers associated with such devices. Due to the challenges of delivering therapeutic agents to the inner ear, bile acids are being explored as potential drug excipients and permeation enhancers. This review, therefore, aims to explore the pathophysiology of hearing loss, the challenges in treatment and the manners in which bile acids could potentially aid in overcoming these challenges.

Microencapsulation of formulation designs further expands the field and offers the potential for use in developing bioartificial organs via cell encapsulation. Combining formulation design and encapsulation requires ideal excipients to be determined. In terms of cell encapsulation, an environment which allows growth and functionality is paramount to ensuring cell survival and incorporation into a bioartificial organ. Hence, excipients are examined for both individual properties and benefits, and compatibility with encapsulated active materials. Polymers are commonly used in microencapsulation, offering protection from the immune system. Bile acids are emerging as a tool to enhance delivery, both biologically and pharmaceutically. Therefore, this review will focus on bile acids and polymers in formulation design via microencapsulation, in the field of bioartificial organ development.

Ototoxicity is the damage to inner ear sensory epithelia due to exposure to certain medications and chemicals. This occurs when toxins enter the tightly controlled inner ear environment inducing hair cell death, resulting in hearing loss. Recent studies have explored hydrogel-based bio-nanotechnologies and new drug delivery formulations to prevent drug-induced hearing loss, with much attention given to administration of antioxidant drugs. Bile acids have been recognized as promising excipients due to their biocompatibility and unique physiochemical properties. As yet bile acids have not been explored in improving drug delivery to the inner ear despite improving drug stability and delivery in other systems and demonstrating positive biological effects in their own right.

Advancement in the prevention of chemotherapy-induced hearing loss has proposed new nano-based delivery matrices that can target inner ear regions most damaged by chemotherapy. Chemotherapy agents (e.g., cisplatin) induce increased reactive oxygen species formation in the inner ear that damage sensory hair cells and result in irreversible hearing impairment. Exogenous antioxidants (e.g., Probucol and metformin) have been shown to block the formation of these reactive oxygen species. Delivery of these drugs in effective concentrations remains a challenge. Microencapsulation in combination with drug excipients provides one technique to effectively deliver these drugs. This paper investigates the use of probucol and metformin in combination with drug excipients for novel, inner ear, delivery.

Aim: Recent studies suggest potential applications of endogenously produced human bile acids as formulation-excipient and drug tissue permeation enhancers in Type 1 diabetes. We aimed to examine the stability, tissue permeation and ex vivo muscle-cell effects of microencapsulated gliclazide (G) incorporated with a primary (chenodeoxycholic acid [CDCA]), a secondary (ursodeoxycholic acid [UDCA]) or a tertiary (taurocholic acid [TCA]) bile acid. Materials & methods: Four formulations made of sodium alginate, CDCA, UDCA and TCA were examined for buoyancy, tissue-enhancing effects ( in vivo) and local ( ex vivo) viability effects. Results & conclusion: CDCA, UDCA and TCA improved buoyancy and cell viability but not tissue-specific uptake. G-TCA-sodium alginate microcapsules exerted hypoglycemic effects, suggesting significant improvement of G gut-uptake by TCA, possibly via improving buoyancy.

Aim: Taurine-conjugated bile acids possess positive formulation-stabilization effects, which are desirable in diabetes treatments. The taurine-conjugated bile acid, taurocholic acid (TCA), has shown promising formulation-stabilizing effects on the delivery of the antioxidant drug, probucol (PB), but success is limited due to its poor release profile. This study aimed to design new PB-TCA formulations using new polymers, and examine antioxidant and antidiabetic effects using β-cells for PB with or without TCA. Materials and methods: Different formulations using alginate-insoluble esters of polymethylacrylate polymers encapsulating PB and TCA were developed, microencapsulated and examined for stability and biological activity. Results: TCA addition to new PB matrices improved osmotic and mechanical properties, and this effect was dependent on polymethylacrylate composition and concentration. Conclusion: TCA can optimize the oral delivery of anti-diabetic compounds.

Aim: Gliclazide (G) is a drug prescribed for Type 2 diabetics, although recent studies suggest it has desirable effects in both types of diabetes, Type 1 diabetes and Type 2 diabetes. G has an inconsistent absorption due to poor formulation and bile acids (BAs) have shown significant promise in drug formulation optimization. Hence, the study aimed to examine G effects on histopathological, anti-inflammatory and antidiabetic effects when encapsulated with BAs. Materials & methods: Rats were randomized into eight groups, of which seven were made Type 1 diabetes and treated with various BA-based treatments. Tissue histopathology, inflammation and the bile acid profile were analyzed. Results & conclusion: G capsules showed no histological but the most anti-inflammatory effects, which suggest significant beneficial effects in diabetes treatment.

Aim: Common features in insulin-resistance diabetes include inflammation and liver damage due to bile acid accumulation. Results & methodology: This study aimed to test in vivo pharmacological effects of combining two drugs, ursodeoxycholic acid that has bile acid regulatory effects, and probucol (PB) that has potent anti-oxidative stress effects, using a new poly(meth)acrylate nano-targeting formulation on prediabetic mice. Mice were made diabetic and were fed daily with either PB, nanoencapsulated PB or nanoencapsulated PB-ursodeoxycholic acid before blood, tissues, urine and feces were collected for inflammation and bile acid measurements. The nanoencapsulated PB-ursodeoxycholic acid formulation increased plasma IL-10, and increased the concentration of primary bile acids in the liver and heart. Conclusion: Results suggest potential applications in regulating IL-10 in insulin-resistance prediabetes.

Deoxycholic acid (DCA) has improved gliclazide oral absorption, while EudragitThe PB formulations were prepared using ED polymers and DCA, and formulations were analyzed for their rheological and biological properties.Rheological properties and size distribution were similar among all groups. β-cell survival and biological activities were best with NM30D microcapsules. The inflammatory profile and oxidative stress effects of microcapsules remained similar among all groups.ED NM30D and DCA incorporation can exert positive and stabilizing effects on PB oral microcapsules.

Aim: Deoxycholic acid (DCA) has improved gliclazide oral absorption, while Eudragit® (ED) polymers have improved formulation stability of antidiabetic drugs. The aim of the study is to test if DCA and ED encapsulation will optimize the release and stability of the potential antidiabetic drug probucol (PB). Materials & methods: The PB formulations were prepared using ED polymers and DCA, and formulations were analyzed for their rheological and biological properties. Results: Rheological properties and size distribution were similar among all groups. β-cell survival and biological activities were best with NM30D microcapsules. The inflammatory profile and oxidative stress effects of microcapsules remained similar among all groups. Conclusion: ED NM30D and DCA incorporation can exert positive and stabilizing effects on PB oral microcapsules.