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Keywords = repaglinide (Rp)

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16 pages, 3868 KiB  
Article
Repaglinide Induces ATF6 Processing and Neuroprotection in Transgenic SOD1G93A Mice
by Rafael Gonzalo-Gobernado, Laura Moreno-Martínez, Paz González, Xose Manuel Dopazo, Ana Cristina Calvo, Isabel Pidal-Ladrón de Guevara, Elisa Seisdedos, Rodrigo Díaz-Muñoz, Britt Mellström, Rosario Osta and José Ramón Naranjo
Int. J. Mol. Sci. 2023, 24(21), 15783; https://doi.org/10.3390/ijms242115783 - 30 Oct 2023
Cited by 4 | Viewed by 2176
Abstract
The interaction of the activating transcription factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a potential therapeutic target in neurodegeneration. Modulation of the [...] Read more.
The interaction of the activating transcription factor 6 (ATF6), a key effector of the unfolded protein response (UPR) in the endoplasmic reticulum, with the neuronal calcium sensor Downstream Regulatory Element Antagonist Modulator (DREAM) is a potential therapeutic target in neurodegeneration. Modulation of the ATF6–DREAM interaction with repaglinide (RP) induced neuroprotection in a model of Huntington’s disease. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure, characterized by the progressive loss of motoneurons resulting in muscle denervation, atrophy, paralysis, and death. The aim of this work was to investigate the potential therapeutic significance of DREAM as a target for intervention in ALS. We found that the expression of the DREAM protein was reduced in the spinal cord of SOD1G93A mice compared to wild-type littermates. RP treatment improved motor strength and reduced the expression of the ALS progression marker collagen type XIXα1 (Col19α1 mRNA) in the quadriceps muscle in SOD1G93A mice. Moreover, treated SOD1G93A mice showed reduced motoneuron loss and glial activation and increased ATF6 processing in the spinal cord. These results indicate that the modulation of the DREAM–ATF6 interaction ameliorates ALS symptoms in SOD1G93A mice. Full article
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18 pages, 5487 KiB  
Article
Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes
by Mubashir Ahmad, Shahzeb Khan, Syed Muhammad Hassan Shah, Muhammad Zahoor, Zahid Hussain, Haya Hussain, Syed Wadood Ali Shah, Riaz Ullah and Amal Alotaibi
Biomedicines 2023, 11(4), 1064; https://doi.org/10.3390/biomedicines11041064 - 1 Apr 2023
Cited by 9 | Viewed by 4104
Abstract
The technologies for fabrication of nanocrystals have an immense potential to improve solubility of a variety of the poor water-soluble drugs with subsequent enhanced bioavailability. Repaglinide (Rp) is an antihyperglycemic drug having low bioavailability due to its extensive first-pass metabolism. Microfluidics is a [...] Read more.
The technologies for fabrication of nanocrystals have an immense potential to improve solubility of a variety of the poor water-soluble drugs with subsequent enhanced bioavailability. Repaglinide (Rp) is an antihyperglycemic drug having low bioavailability due to its extensive first-pass metabolism. Microfluidics is a cutting-edge technique that provides a new approach for producing nanoparticles (NPs) with controlled properties for a variety of applications. The current study’s goal was to engineer repaglinide smart nanoparticles (Rp-Nc) utilizing microfluidic technology (Dolomite Y shape), and then to perform in-vitro, in-vivo, and toxicity evaluations of them. This method effectively generated nanocrystals with average particle sizes of 71.31 ± 11 nm and a polydispersity index (PDI) of 0.072 ± 12. The fabricated Rp’s crystallinity was verified by Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD). In comparison to the raw and commercially available tablets, the fabricated Rp’s nanoparticles resulted in a higher saturation solubility and dissolving rate (p < 0.05). Rp nanocrystals had a considerably lower (p < 0.05) IC50 value than that of the raw drug and commercial tablets. Moreover, Rp nanocrystals at the 0.5 and 1 mg/kg demonstrated a significant decrease in blood glucose level (mg/dL, p < 0.001, n = 8) compared to its counterparts. Rp nanocrystals at the 0.5 mg/kg demonstrated a significant decrease (p < 0.001, n = 8) in blood glucose compared to its counterparts at a dose of 1 mg/kg. The selected animal model’s histological analyses and the effect of Rp nanocrystals on several internal organs were determined to be equivalent to those of the control animal group. The findings of the present study indicated that nanocrystals of Rp with improved anti-diabetic properties and safety profiles can be successfully produced using controlled microfluidic technology, an innovative drug delivery system (DDS) approach. Full article
(This article belongs to the Special Issue Bio-Nano Interfaces: From Biosensors to Nanomedicines)
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