Oral gavage of nano-encapsulated conjugated acrylic acid-bile acid formulation in type 1 diabetes altered pharmacological profile of bile acids, and improved glycaemia and suppressed inflammation

Mooranian, Armin; Zamani, Nassim; Ionescu, Corina Mihaela; Takechi, Ryusuke; Luna, Giuseppe Antonio Di; Mikov, Momir; Goločorbin-Kon, Svetlana; Kovačević, Božica; Al‐Salami, Hani

doi:10.1007/s43440-019-00030-z

Cited by 20 publications

(20 citation statements)

References 51 publications

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“…Briefly, CDCA microcapsules were prepared using our Ionic Gelation Vibrational Jet Flow technology via ionotropic gelation processed using main encapsulating parameters, based on Büchi customized technology (Büchi, Switzerland) [ 30 , 40 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. A multitude of topographic assessments were conducted, with microscopy imaging, surface spectral analyses and CDCA surface distribution assessments, scanning electron imaging, energy dispersive X-ray spectroscopy, and confocal image measurements; all of which were carried out on three randomly selected batches at the John De Laeter center, as well as at the Curtin Health Innovation Research Institute (Bentley, WA, Australia).…”

Section: Methodsmentioning

confidence: 99%

Chenodeoxycholic Acid Pharmacology in Biotechnology and Transplantable Pharmaceutical Applications for Tissue Delivery: An Acute Preclinical Study

Mooranian

Ionescu

Wagle

et al. 2021

Cells

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Introduction. Primary bile acids (PBAs) are produced and released into human gut as a result of cholesterol catabolism in the liver. A predominant PBA is chenodeoxycholic acid (CDCA), which in a recent study in our laboratory, showed significant excipient-stabilizing effects on microcapsules carrying insulinoma β-cells, in vitro, resulting in improved cell functions and insulin release, in the hyperglycemic state. Hence, this study aimed to investigate the applications of CDCA in bio-encapsulation and transplantation of primary healthy viable islets, preclinically, in type 1 diabetes. Methods. Healthy islets were harvested from balb/c mice, encapsulated in CDCA microcapsules, and transplanted into the epididymal tissues of 6 syngeneic diabetic mice, post diabetes confirmation. Pre-transplantation, the microcapsules’ morphology, size, CDCA-deep layer distribution, and physical features such as swelling ratio and mechanical strength were analyzed. Post-transplantation, animals’ weight, bile acids’, and proinflammatory biomarkers’ concentrations were analyzed. The control group was diabetic mice that were transplanted encapsulated islets (without PBA). Results and Conclusion. Islet encapsulation by PBA microcapsules did not compromise the microcapsules’ morphology or features. Furthermore, the PBA-graft performed better in terms of glycemic control and resulted in modulation of the bile acid profile in the brain. This is suggestive that the improved glycemic control was mediated via brain-related effects. However, the improvement in graft insulin delivery and glycemic control was short-term.

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Section: Methodsmentioning

confidence: 99%

Chenodeoxycholic Acid Pharmacology in Biotechnology and Transplantable Pharmaceutical Applications for Tissue Delivery: An Acute Preclinical Study

Mooranian

Ionescu

Wagle

et al. 2021

Cells

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“…Microencapsulation of cells was achieved with the Büchi Ionic Gelation Vibrational Jet Flow technology system with methods previously established in our laboratory [ 29 , 31 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]. Briefly, by using concentrations of 1.5 × 10 6 cells/mL as the encapsulating medium, freshly resuspended cells were mixed with an encapsulating hydrogel-polymer system in a 1:1 ratio, whereby the mixture was then used to produce cell-loaded microcapsules via vibrational jet flow technology, coupled with frequency-modulated laminar jet flow [ 59 ].…”

Section: Methodsmentioning

confidence: 99%

“…Using Dulbecco’s modified eagle medium (Gibco Life Technologies, USA) NIT-1 [ 60 ] cells were grown in 25 cm 2 flasks (Thermo Fisher Scientific, Melbourne, Victoria, Australia). The medium also contained 5% penicillin-streptomycin (Thermo Fisher Scientific, Melbourne, Victoria, Australia) and 10% foetal bovine serum [ 8 , 49 , 50 ].…”

Section: Methodsmentioning

confidence: 99%

“…The Seahorse Flux Analyser XF 96 (Seahorse Bioscience, North Billerica, MA, USA) was used to measure various mitochondrial parameters in real time assays using a method developed by the laboratory [ 8 , 49 , 50 ]. Parameters measured included: extracellular acidification rate (ECAR), oxygen consumption rate (OCR), proton production rate (PPR), ATP production (ATPP), Basal Respiration (BR), Coupling Efficiency (CE), Maximum Respiration (MR), Glycolysis (G), Non-Mitochondria-OCR (NM-OCR), non-glucose-derived extracellular acidification rate (NGD-ECAR), Spare Respiratory Capacity (SRC), and Proton Leak (PL).…”

Section: Methodsmentioning

confidence: 99%

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Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

et al. 2021

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Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

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“…Finally, UDCA treatment significantly downregulated miR-34 expression and significantly reduced the cell death of miR-34-transfected cells [ 182 ]. UDCA incorporation into nano and micro capsule for drug delivery has demonstrated improved permeability [ 147 ] cytoprotective effects [ 183 ], and antioxidant effects [ 92 , 135 , 146 , 184 , 185 , 186 , 187 , 188 ].…”

Section: Bile Acidsmentioning

confidence: 99%

A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

et al. 2021

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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.

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Oral gavage of nano-encapsulated conjugated acrylic acid-bile acid formulation in type 1 diabetes altered pharmacological profile of bile acids, and improved glycaemia and suppressed inflammation

Cited by 20 publications

References 51 publications

Chenodeoxycholic Acid Pharmacology in Biotechnology and Transplantable Pharmaceutical Applications for Tissue Delivery: An Acute Preclinical Study

Chenodeoxycholic Acid Pharmacology in Biotechnology and Transplantable Pharmaceutical Applications for Tissue Delivery: An Acute Preclinical Study

Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

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