Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes

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....

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Main Authors: Mubashir Ahmad, Shahzeb Khan, Syed Muhammad Hassan Shah, Muhammad Zahoor, Zahid Hussain, Haya Hussain, Syed Wadood Ali Shah, Riaz Ullah, Amal Alotaibi
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/4/1064
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author Mubashir Ahmad
Shahzeb Khan
Syed Muhammad Hassan Shah
Muhammad Zahoor
Zahid Hussain
Haya Hussain
Syed Wadood Ali Shah
Riaz Ullah
Amal Alotaibi
author_facet Mubashir Ahmad
Shahzeb Khan
Syed Muhammad Hassan Shah
Muhammad Zahoor
Zahid Hussain
Haya Hussain
Syed Wadood Ali Shah
Riaz Ullah
Amal Alotaibi
author_sort Mubashir Ahmad
collection DOAJ
description 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 (<i>p</i> < 0.05). Rp nanocrystals had a considerably lower (<i>p</i> < 0.05) IC<sub>50</sub> 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, <i>p</i> < 0.001, <i>n</i> = 8) compared to its counterparts. Rp nanocrystals at the 0.5 mg/kg demonstrated a significant decrease (<i>p</i> < 0.001, <i>n</i> = 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.
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spelling doaj.art-08bb7ffb59d04eb48ea4fee621340f542023-11-17T18:26:02ZengMDPI AGBiomedicines2227-90592023-04-01114106410.3390/biomedicines11041064Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of DiabetesMubashir Ahmad0Shahzeb Khan1Syed Muhammad Hassan Shah2Muhammad Zahoor3Zahid Hussain4Haya Hussain5Syed Wadood Ali Shah6Riaz Ullah7Amal Alotaibi8Department of Pharmacy, University of Malakand, Chakdara 18800, PakistanCenter for Pharmaceutical Engineering Science, Faculty of Life Sciences, School of Pharmacy and Medical Sciences, University of Bradford, Bradford BD7 1DP, UKDepartment of Pharmacy, Sarhad University of Science and Information Technology, Peshawar 18500, PakistanDepartment of Biochemistry, University of Malakand, Chakdara 18800, PakistanDepartment of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab EmiratesDepartment of Pharmacy, Shaheed Benazir Bhutto University, Sheringal Dir 18000, PakistanDepartment of Pharmacy, University of Malakand, Chakdara 18800, PakistanMedicinal Aromatic and Poisonous Plants Research Center, Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Basic Science, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi ArabiaThe 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 (<i>p</i> < 0.05). Rp nanocrystals had a considerably lower (<i>p</i> < 0.05) IC<sub>50</sub> 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, <i>p</i> < 0.001, <i>n</i> = 8) compared to its counterparts. Rp nanocrystals at the 0.5 mg/kg demonstrated a significant decrease (<i>p</i> < 0.001, <i>n</i> = 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.https://www.mdpi.com/2227-9059/11/4/1064repaglinide (Rp)microfluidic technologyin-vitroin-vivo studybioavailabilityrats
spellingShingle Mubashir Ahmad
Shahzeb Khan
Syed Muhammad Hassan Shah
Muhammad Zahoor
Zahid Hussain
Haya Hussain
Syed Wadood Ali Shah
Riaz Ullah
Amal Alotaibi
Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes
Biomedicines
repaglinide (Rp)
microfluidic technology
in-vitro
in-vivo study
bioavailability
rats
title Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes
title_full Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes
title_fullStr Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes
title_full_unstemmed Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes
title_short Formulation and Optimization of Repaglinide Nanoparticles Using Microfluidics for Enhanced Bioavailability and Management of Diabetes
title_sort formulation and optimization of repaglinide nanoparticles using microfluidics for enhanced bioavailability and management of diabetes
topic repaglinide (Rp)
microfluidic technology
in-vitro
in-vivo study
bioavailability
rats
url https://www.mdpi.com/2227-9059/11/4/1064
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