Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles

Bader B Alsulays,1 Md Khalid Anwer,1 Gamal A Soliman,2,3 Sultan M Alshehri,4 El-Sayed Khafagy1,5 1Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; 2Department of Pharmacology, College of Veterinary Medicine, Cairo University, Cai...

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Autores principales:	Alsulays BB, Anwer MK, Soliman GA, Alshehri SM, Khafagy ES
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	cell-penetrating peptides penetratin stereochemistry solid lipid nanoparticles oral insulin administration enzymatic degradation bioavailability. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d3efdc65ef0c4e9c85867f41328baced
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spelling	oai:doaj.org-article:d3efdc65ef0c4e9c85867f41328baced2021-12-02T02:39:41ZImpact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles1178-2013https://doaj.org/article/d3efdc65ef0c4e9c85867f41328baced2019-11-01T00:00:00Zhttps://www.dovepress.com/impact-of-penetratin-stereochemistry-on-the-oral-bioavailability-of-in-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Bader B Alsulays,1 Md Khalid Anwer,1 Gamal A Soliman,2,3 Sultan M Alshehri,4 El-Sayed Khafagy1,5 1Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; 2Department of Pharmacology, College of Veterinary Medicine, Cairo University, Cairo 12211, Egypt; 3Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj 11942, Saudi Arabia; 4Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 5Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 415-22, EgyptCorrespondence: El-Sayed KhafagyDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, PO Box 173, AlKharj 11942, Saudi ArabiaTel +966 533564286Fax +966 115886001Email e.khafagy@psau.edu.saPurpose: This study evaluated the stereoisomeric effect of L- and D-penetratin—cell-penetrating peptides (CPPs)—incorporated insulin-loaded solid lipid nanoparticles (INS-SLNs) on the bioavailability (BA) of oral insulin (INS).Methods: Insulin-loaded solid nanoparticles, L-penetratin-INS-SLNs (LP-INS-SLNs), and D-penetratin-INS-SLNs (DP-INS-SLNs) were formulated by double emulsification. The developed SLNs were evaluated for particle size, zeta potential (ZP), and drug encapsulation and subjected to differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and evaluated for stability against enzymatic degradation in rat intestinal fluid. Finally, the SLNs were administered to rats to evaluate the BA of INS-SLNs that contained L- and D-penetratin.Results: The mean particle size, PDI, and ZP values of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 618.5 to 973.0 nm, 0.227 to 0.734, and −17.0 to −23.7 mV, respectively. The encapsulation efficiency (%EE) and drug loading (%DL) of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 59.03% to 67.42% and from 1.62% to 1.82%, respectively. Differential scanning calorimetry and FTIR analyses indicated that INS was successfully encapsulated in SLNs. Enzymatic degradation of DP-INS-SLNs was slower in intestinal fluid, and the half-life (t1/2) was significantly prolonged, compared to all other SLNs. The pharmacological availability (PA) and BA of orally administered LP-INS-SLNs, which were the most effective SLNs, were 13.1% and 15.7% relative to s.c. administration, respectively.Conclusion: Penetratin stereochemistry significantly impacted oral BA of INS-SLNs, which are promising carriers for oral INS administration.Keywords: cell-penetrating peptides, penetratin, stereochemistry, solid lipid nanoparticles, enzymatic degradation, oral insulin bioavailabilityAlsulays BBAnwer MKSoliman GAAlshehri SMKhafagy ESDove Medical Pressarticlecell-penetrating peptidespenetratinstereochemistrysolid lipid nanoparticlesoral insulin administrationenzymatic degradationbioavailability.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 9127-9138 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell-penetrating peptides penetratin stereochemistry solid lipid nanoparticles oral insulin administration enzymatic degradation bioavailability. Medicine (General) R5-920
spellingShingle	cell-penetrating peptides penetratin stereochemistry solid lipid nanoparticles oral insulin administration enzymatic degradation bioavailability. Medicine (General) R5-920 Alsulays BB Anwer MK Soliman GA Alshehri SM Khafagy ES Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles
description	Bader B Alsulays,1 Md Khalid Anwer,1 Gamal A Soliman,2,3 Sultan M Alshehri,4 El-Sayed Khafagy1,5 1Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; 2Department of Pharmacology, College of Veterinary Medicine, Cairo University, Cairo 12211, Egypt; 3Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, AlKharj 11942, Saudi Arabia; 4Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 5Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 415-22, EgyptCorrespondence: El-Sayed KhafagyDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, PO Box 173, AlKharj 11942, Saudi ArabiaTel +966 533564286Fax +966 115886001Email e.khafagy@psau.edu.saPurpose: This study evaluated the stereoisomeric effect of L- and D-penetratin—cell-penetrating peptides (CPPs)—incorporated insulin-loaded solid lipid nanoparticles (INS-SLNs) on the bioavailability (BA) of oral insulin (INS).Methods: Insulin-loaded solid nanoparticles, L-penetratin-INS-SLNs (LP-INS-SLNs), and D-penetratin-INS-SLNs (DP-INS-SLNs) were formulated by double emulsification. The developed SLNs were evaluated for particle size, zeta potential (ZP), and drug encapsulation and subjected to differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and evaluated for stability against enzymatic degradation in rat intestinal fluid. Finally, the SLNs were administered to rats to evaluate the BA of INS-SLNs that contained L- and D-penetratin.Results: The mean particle size, PDI, and ZP values of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 618.5 to 973.0 nm, 0.227 to 0.734, and −17.0 to −23.7 mV, respectively. The encapsulation efficiency (%EE) and drug loading (%DL) of INS-SLNs, LP-INS-SLNs, and DP-INS-SLNs ranged from 59.03% to 67.42% and from 1.62% to 1.82%, respectively. Differential scanning calorimetry and FTIR analyses indicated that INS was successfully encapsulated in SLNs. Enzymatic degradation of DP-INS-SLNs was slower in intestinal fluid, and the half-life (t1/2) was significantly prolonged, compared to all other SLNs. The pharmacological availability (PA) and BA of orally administered LP-INS-SLNs, which were the most effective SLNs, were 13.1% and 15.7% relative to s.c. administration, respectively.Conclusion: Penetratin stereochemistry significantly impacted oral BA of INS-SLNs, which are promising carriers for oral INS administration.Keywords: cell-penetrating peptides, penetratin, stereochemistry, solid lipid nanoparticles, enzymatic degradation, oral insulin bioavailability
format	article
author	Alsulays BB Anwer MK Soliman GA Alshehri SM Khafagy ES
author_facet	Alsulays BB Anwer MK Soliman GA Alshehri SM Khafagy ES
author_sort	Alsulays BB
title	Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles
title_short	Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles
title_full	Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles
title_fullStr	Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles
title_full_unstemmed	Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles
title_sort	impact of penetratin stereochemistry on the oral bioavailability of insulin-loaded solid lipid nanoparticles
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/d3efdc65ef0c4e9c85867f41328baced
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_version_	1718402317616676864

Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles

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