Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study

Alaa Mohamed Nazief,1 Passainte Saber Hassaan,2 Hoda Mahmoud Khalifa,3 Magda Samir Sokar,1 Amal Hassan El-Kamel1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egy...

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Autores principales:	Nazief AM, Hassaan PS, Khalifa HM, Sokar MS, El-Kamel AH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	gliclazide lipid nanoparticles bioavailability safety Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a974907dc9af4c449c327a4787f1b036
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spelling	oai:doaj.org-article:a974907dc9af4c449c327a4787f1b0362021-12-02T07:19:33ZLipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study1178-2013https://doaj.org/article/a974907dc9af4c449c327a4787f1b0362020-02-01T00:00:00Zhttps://www.dovepress.com/lipid-based-gliclazide-nanoparticles-for-treatment-of-diabetes-formula-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Alaa Mohamed Nazief,1 Passainte Saber Hassaan,2 Hoda Mahmoud Khalifa,3 Magda Samir Sokar,1 Amal Hassan El-Kamel1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 3Department of Histology and Cell Biology, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Amal Hassan El-KamelDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptTel +201005080510Email amalelkamel@yahoo.comIntroduction: Solid lipid nanoparticles (SLNs) are considered a promising system in enhancing the oral bioavailability of poorly water-soluble drugs; owing to their intrinsic ability to increase the solubility together with protecting the incorporated drugs from extensive metabolism.Objective: Exploiting such properties, SLNs loaded with gliclazide (GLZ) were developed in an attempt to improve the oral bioavailability and the anti-diabetic action of GLZ, together with prolonging its duration of action for better glycemic control.Methods: SLNs were prepared by ultra-sonication technique using glyceryl behenate (Compritol® 888 ATO) as a lipid matrix and poloxamer 188 (PLX) as a stabilizer. A 2*3 asymmetrical factorial design was adopted to study the effect of different stabilizer concentrations at different sonication times on the shape, and size of the particles, PDI and drug loading. The selected optimum formulation was then freeze dried using trehalose di-hydrate as a cryo-protectant in different ratios with respect to glyceryl behenate concentration. After freeze drying, the formulation was tested for in-vitro drug release, pharmacokinetics, and pharmacodynamics. Safety of the selected formula was established after carrying out a subacute toxicity study.Results: The factorial design experiment resulted in an optimum formulation coded 10F2 (150 mg PLX/10 min sonication). Scanning electron micrographs showed spherical particles with smooth surface, whereas a ratio of 2:1 cryo-protectant:lipid was found to be optimum with particle size of 245.9 ± 26.2 nm, polydispersity index of 0.482 ± 0.026, and biphasic in-vitro release with an initial burst effect, followed by a prolonged release phase. On the other hand, the selected SLNs exhibited prolonged drug release when compared with the GLZ commercial immediate release (IR) tablets (Diamicron®). Pharmacokinetics study showed about 5-fold increase in GLZ oral bioavailability loaded in SLNs when compared with raw GLZ powder. Pharmacodynamics study on a diabetic rat model confirmed the better anti-diabetic action of GLZ loaded SLNs when compared to raw GLZ powder. Subacute toxicity study indicated the safety of SLNs upon repetitive oral administration.Keywords: gliclazide, lipid nanoparticles, bioavailability, safetyNazief AMHassaan PSKhalifa HMSokar MSEl-Kamel AHDove Medical Pressarticlegliclazidelipid nanoparticlesbioavailabilitysafetyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1129-1148 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	gliclazide lipid nanoparticles bioavailability safety Medicine (General) R5-920
spellingShingle	gliclazide lipid nanoparticles bioavailability safety Medicine (General) R5-920 Nazief AM Hassaan PS Khalifa HM Sokar MS El-Kamel AH Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study
description	Alaa Mohamed Nazief,1 Passainte Saber Hassaan,2 Hoda Mahmoud Khalifa,3 Magda Samir Sokar,1 Amal Hassan El-Kamel1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 3Department of Histology and Cell Biology, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Amal Hassan El-KamelDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, EgyptTel +201005080510Email amalelkamel@yahoo.comIntroduction: Solid lipid nanoparticles (SLNs) are considered a promising system in enhancing the oral bioavailability of poorly water-soluble drugs; owing to their intrinsic ability to increase the solubility together with protecting the incorporated drugs from extensive metabolism.Objective: Exploiting such properties, SLNs loaded with gliclazide (GLZ) were developed in an attempt to improve the oral bioavailability and the anti-diabetic action of GLZ, together with prolonging its duration of action for better glycemic control.Methods: SLNs were prepared by ultra-sonication technique using glyceryl behenate (Compritol® 888 ATO) as a lipid matrix and poloxamer 188 (PLX) as a stabilizer. A 2*3 asymmetrical factorial design was adopted to study the effect of different stabilizer concentrations at different sonication times on the shape, and size of the particles, PDI and drug loading. The selected optimum formulation was then freeze dried using trehalose di-hydrate as a cryo-protectant in different ratios with respect to glyceryl behenate concentration. After freeze drying, the formulation was tested for in-vitro drug release, pharmacokinetics, and pharmacodynamics. Safety of the selected formula was established after carrying out a subacute toxicity study.Results: The factorial design experiment resulted in an optimum formulation coded 10F2 (150 mg PLX/10 min sonication). Scanning electron micrographs showed spherical particles with smooth surface, whereas a ratio of 2:1 cryo-protectant:lipid was found to be optimum with particle size of 245.9 ± 26.2 nm, polydispersity index of 0.482 ± 0.026, and biphasic in-vitro release with an initial burst effect, followed by a prolonged release phase. On the other hand, the selected SLNs exhibited prolonged drug release when compared with the GLZ commercial immediate release (IR) tablets (Diamicron®). Pharmacokinetics study showed about 5-fold increase in GLZ oral bioavailability loaded in SLNs when compared with raw GLZ powder. Pharmacodynamics study on a diabetic rat model confirmed the better anti-diabetic action of GLZ loaded SLNs when compared to raw GLZ powder. Subacute toxicity study indicated the safety of SLNs upon repetitive oral administration.Keywords: gliclazide, lipid nanoparticles, bioavailability, safety
format	article
author	Nazief AM Hassaan PS Khalifa HM Sokar MS El-Kamel AH
author_facet	Nazief AM Hassaan PS Khalifa HM Sokar MS El-Kamel AH
author_sort	Nazief AM
title	Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study
title_short	Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study
title_full	Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study
title_fullStr	Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study
title_full_unstemmed	Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study
title_sort	lipid-based gliclazide nanoparticles for treatment of diabetes: formulation, pharmacokinetics, pharmacodynamics and subacute toxicity study
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/a974907dc9af4c449c327a4787f1b036
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Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study

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