An advanced microencapsulated system: a platform for optimized oral delivery of antidiabetic drug-bile acid formulations

Mooranian, Armin; Negrulj, Rebecca; Mathavan, Sangeetha; Martinez, Jorge; Sciarretta, Jessica; Chen-Tan, Nigel; Mukkur, T.K.S.; Mikov, Momir; Lalić-Popović, Mladena; Stojančević, Maja; Goločorbin-Kon, Svetlana; Al‐Salami, Hani

doi:10.3109/10837450.2014.915570

Cited by 57 publications

(59 citation statements)

References 25 publications

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“…The TCA powder analysis (Figure 5a) shows identical peaks to previously published work and confirms the presence of TCA (Mooranian et al, 2014g). Figure 5(b) shows the presence of a carbonyl group for G by exhibiting a sharp concave peak at 1785.13 cm À1 , as well as the presence of sulfonyl group (R-S(¼O) 2 -R 0 ).…”

Section: Chemical Stability Studiessupporting

confidence: 72%

“…Overall, the DSC results (Table 2) suggest that the endothermic shift in melting points of G and SA pre-and post-microencapsulation may arise due to ionic interferences within the polymer matrix. In addition, it is evident from all the spectra obtained that there are no significant interactions between the drug and its excipients, suggesting compatibility (Mooranian et al, 2014f). Accordingly, DSC results show that the thermal stability of G has been maintained throughout the microencapsulation process and this was further confirmed by chemical stability studies using FTIR analysis ( Figure 5).…”

Section: Thermal Stability Studiessupporting

confidence: 54%

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A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

et al. 2015

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Context: Gliclazide (G) is a commonly prescribed drug for Type 2 diabetes (T2D). In a recent study, we found that when G was combined with a primary bile acid, and gavaged to an animal model of Type 1 diabetes (T1D), it exerted a hypoglycemic effect. We hypothesized this to be due to metabolic activation of the primary bile acid into a secondary or a tertiary bile acid, which enhanced G solubility and absorption. The tertiary bile acid, taurocholic acid (TCA), has shown strong permeation-enhancing effects in vivo. Thus, we aimed to design, characterize, and test microcapsules incorporating G and TCA in an animal model of T1D. Methods: Microcapsules were prepared using the polymer sodium alginate (SA). G-SA microcapsules (control) and G-TCA-SA microcapsules (test) were extensively examined (in-vitro) at different pH and temperatures. The microcapsules were gavaged to diabetic rats, and blood glucose and G concentrations in serum were examined. Ex-vivo studies were also performed using a muscle cell line (C2C12), and cell viability and glucose intake post-treatment were examined. Results: G-TCA-SA microcapsules showed good stability, uniformity, and thermal and chemical excipient compatibilities. TCA did not change the size or the shape of the microcapsules, but it enhanced their mechanical resistance and reduced their swelling properties. G-TCA-SA enhanced the viability of C2C12 cells over 24 hours, and exerted a hypoglycemic effect in alloxan-induced type-1 diabetic rats. Conclusions: The incorporation of TCA into G-microcapsules resulted in functionally improved microcapsules with a positive effect on cell viability and glycemic control in Type-1 diabetic animals.

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Section: Chemical Stability Studiessupporting

confidence: 72%

Section: Thermal Stability Studiessupporting

confidence: 54%

A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

et al. 2015

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“…Such delivery-based mechanisms of synergy are well characterized in the drug development field, where facilitated delivery formulations are widespread (63). Indeed, it is commonplace to employ cholate for micelle-based delivery of hydrophobic drugs (64,65). However, in contrast to the intentional formulation of cholate-based delivery formulations, the interaction we observed here is unique in that it contributes to a naturally occurring solubility switch.…”

Section: Discussionmentioning

confidence: 99%

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

et al. 2016

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bSalmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.

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“…To determine the swelling properties of the microcapsules (SA and PB-SA), 50-mg dry microcapsules were weighed and placed in 20 mL of two pH values (3 and 7.8) and two temperatures (25 and 37°C) for 6 h. The selection of the two temperatures, pH values and study duration was based on our previously published work (14,15). The swollen microcapsules were then removed at periodically predetermined intervals (hourly).…”

Section: Characterisation Of Pb-loaded Microcapsulesmentioning

confidence: 99%

Probucol Release from Novel Multicompartmental Microcapsules for the Oral Targeted Delivery in Type 2 Diabetes

et al. 2014

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Abstract. In previous studies, we developed and characterised multicompartmental microcapsules as a platform for the targeted oral delivery of lipophilic drugs in type 2 diabetes (T2D). We also designed a new microencapsulated formulation of probucol-sodium alginate (PB-SA), with good structural properties and excipient compatibility. The aim of this study was to examine the stability and pH-dependent targeted release of the microcapsules at various pH values and different temperatures. Microencapsulation was carried out using a Büchi-based microencapsulating system developed in our laboratory. Using SA polymer, two formulations were prepared: empty SA microcapsules (SA, control) and loaded SA microcapsules (PB-SA, test), at a constant ratio (1:30), respectively. Microcapsules were examined for drug content, zeta potential, size, morphology and swelling characteristics and PB release characteristics at pH 1.5, 3, 6 and 7.8. The production yield and microencapsulation efficiency were also determined. PB-SA microcapsules had 2.6±0.25% PB content, and zeta potential of −66±1.6%, suggesting good stability. They showed spherical and uniform morphology and significantly higher swelling at pH 7.8 at both 25 and 37°C (p<0.05). The microcapsules showed multiphasic release properties at pH 7.8. The production yield and microencapsulation efficiency were high (85±5 and 92±2%, respectively). The PB-SA microcapsules exhibited distal gastrointestinal tract targeted delivery with a multiphasic release pattern and with good stability and uniformity. However, the release of PB from the microcapsules was not controlled, suggesting uneven distribution of the drug within the microcapsules.

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An advanced microencapsulated system: a platform for optimized oral delivery of antidiabetic drug-bile acid formulations

Abstract: The new microencapsulated-formulation has good and uniform structural properties and may be suitable for oral delivery of antidiabetic-bile acid formulations.

Cited by 57 publications

References 25 publications

A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

Probucol Release from Novel Multicompartmental Microcapsules for the Oral Targeted Delivery in Type 2 Diabetes

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