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. Nanogels showed a high level of biocompatibility after 24-hour exposure to auditory and macrophage cell lines, with minimal cytotoxicity compared to untreated control. Incubation with nanogels did not alter cellular respiration and glycolysis of the auditory cell line but showed possible mitochondrial dysfunction in macrophages, suggesting tissue-dependent effects of bile acids. Bile acid-nanogels had minimal impact on intracellular reactive oxygen species, with LCA demonstrating the most pro-oxidative behaviour. This study suggests that thermoresponsive nanogels with bile acid, particularly DCA and UDCA, may be promising candidates for inner ear drug delivery.

Bile acid bio-nanoencapsulation improved drug targeted-delivery and pharmacological effects via cellular flux: 6-months diabetes preclinical study.

The antilipidemic drug, probucol (PB), has demonstrated potential applications in Type 2 diabetes (T2D) through its protective effects on pancreatic ß-cells. PB has poor solubility and bioavailability, and despite attempts to improve its oral delivery, none has shown dramatic improvements in absorption or antidiabetic effects. Preliminary data has shown potential benefits from bile acid co-encapsulation with PB. One bile acid has shown best potential improvement of PB oral delivery (ursodeoxycholic acid, UDCA). This study aimed to examine PB and UDCA microcapsules (with UDCA microcapsules serving as control) in terms of the microcapsules' morphology, biological effects ex vivo, and their hypoglycemic and antilipidemic and anti-inflammatory effects in vivo. PBUDCA and UDCA microcapsules were examined in vitro (formulation studies), ex vivo and in vivo. PBUDCA microcapsules exerted positive effects on ß-cells viability at hyperglycemic state, and brought about hypoglycemic and anti-inflammatory effects on the prediabetic mice. In conclusion, PBUDCA co-encapsulation have showed beneficial therapeutic impact of dual antioxidant-bile acid effects in diabetes treatment.