Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus

An iron-based SBA-16 mesoporous silica (ferrisilicate) with a large surface area and three-dimensional (3D) pores is explored as a potential insulin delivery vehicle with improved encapsulation and loading efficiency. Fe was incorporated into a framework of ferrisilicate using the isomorphous substi...

Full description

Bibliographic Details
Main Authors: B. Rabindran Jermy, Mohammed Salahuddin, Gazali Tanimu, Hatim Dafalla, Sarah Almofty, Vijaya Ravinayagam
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/2/593
_version_ 1797618662549487616
author B. Rabindran Jermy
Mohammed Salahuddin
Gazali Tanimu
Hatim Dafalla
Sarah Almofty
Vijaya Ravinayagam
author_facet B. Rabindran Jermy
Mohammed Salahuddin
Gazali Tanimu
Hatim Dafalla
Sarah Almofty
Vijaya Ravinayagam
author_sort B. Rabindran Jermy
collection DOAJ
description An iron-based SBA-16 mesoporous silica (ferrisilicate) with a large surface area and three-dimensional (3D) pores is explored as a potential insulin delivery vehicle with improved encapsulation and loading efficiency. Fe was incorporated into a framework of ferrisilicate using the isomorphous substitution technique for direct synthesis. Fe<sup>3+</sup> species were identified using diffuse reflectance spectroscopy. The large surface area (804 m<sup>2</sup>/g), cubic pores (3.2 nm) and insulin loading were characterized using XRD, BET surface area, FTIR and TEM analyses. For pH sensitivity, the ferrisilicate was wrapped with polyethylene glycol (MW = 400 Daltons) (PEG). For comparison, Fe (10 wt%) was impregnated on a Korea Advanced Institute of Science and Technology Number 6 (KIT-6) sieve and Mesocellular Silica Foam (MSU-F). Insulin loading was optimized, and its release mechanism was studied using the dialysis membrane technique (MWCO = 14,000 Da) at physiological pH = 7.4, 6.8 and 1.2. The kinetics of the drug’s release was studied using different structured/insulin nanoformulations, including Santa Barbara Amorphous materials (SBA-15, SBA-16), MSU-F, ultra-large-pore FDU-12 (ULPFDU-12) and ferrisilicates. A different insulin adsorption times (0.08–1 h), insulin/ferrisilicate ratios (0.125–1.0) and drug release rates at different pH were examined using the Korsmeyer–Peppas model. The rate of drug release and the diffusion mechanisms were obtained based on the release constant (k) and release exponent (n). The cytotoxicity of the nanoformulation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using human foreskin fibroblast (HFF-1) cells. A low cytotoxicity was observed for this nanoformulation starting at the highest concentrations used, namely, 400 and 800 μg. The hypoglycemic activity of insulin/ferrisilicate/PEG on acute administration in Wistar rats was studied using doses of 2, 5 and 10 mg/kg body weight. The developed facile ferrisilicate/PEG nanoformulation showed a high insulin encapsulation and loading capacity with pH-sensitive insulin release for potential delivery through the oral route.
first_indexed 2024-03-11T08:16:44Z
format Article
id doaj.art-43e25455f5fa489ba0739ac4ad279c88
institution Directory Open Access Journal
issn 1999-4923
language English
last_indexed 2024-03-11T08:16:44Z
publishDate 2023-02-01
publisher MDPI AG
record_format Article
series Pharmaceutics
spelling doaj.art-43e25455f5fa489ba0739ac4ad279c882023-11-16T22:42:01ZengMDPI AGPharmaceutics1999-49232023-02-0115259310.3390/pharmaceutics15020593Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic MellitusB. Rabindran Jermy0Mohammed Salahuddin1Gazali Tanimu2Hatim Dafalla3Sarah Almofty4Vijaya Ravinayagam5Department of NanoMedicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaDepartment of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaCenter for Refining and Advanced Chemicals, Research Institute, King Fahd University of Petroleum and Minerals, P.O. Box 5040, Dhahran 31261, Saudi ArabiaCore Research Facilities (CRF), King Fahd University of Petroleum and Minerals, P.O. Box 613, Dhahran 31261, Saudi ArabiaDepartment of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaDeanship of Scientific Research & Department of NanoMedicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaAn iron-based SBA-16 mesoporous silica (ferrisilicate) with a large surface area and three-dimensional (3D) pores is explored as a potential insulin delivery vehicle with improved encapsulation and loading efficiency. Fe was incorporated into a framework of ferrisilicate using the isomorphous substitution technique for direct synthesis. Fe<sup>3+</sup> species were identified using diffuse reflectance spectroscopy. The large surface area (804 m<sup>2</sup>/g), cubic pores (3.2 nm) and insulin loading were characterized using XRD, BET surface area, FTIR and TEM analyses. For pH sensitivity, the ferrisilicate was wrapped with polyethylene glycol (MW = 400 Daltons) (PEG). For comparison, Fe (10 wt%) was impregnated on a Korea Advanced Institute of Science and Technology Number 6 (KIT-6) sieve and Mesocellular Silica Foam (MSU-F). Insulin loading was optimized, and its release mechanism was studied using the dialysis membrane technique (MWCO = 14,000 Da) at physiological pH = 7.4, 6.8 and 1.2. The kinetics of the drug’s release was studied using different structured/insulin nanoformulations, including Santa Barbara Amorphous materials (SBA-15, SBA-16), MSU-F, ultra-large-pore FDU-12 (ULPFDU-12) and ferrisilicates. A different insulin adsorption times (0.08–1 h), insulin/ferrisilicate ratios (0.125–1.0) and drug release rates at different pH were examined using the Korsmeyer–Peppas model. The rate of drug release and the diffusion mechanisms were obtained based on the release constant (k) and release exponent (n). The cytotoxicity of the nanoformulation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using human foreskin fibroblast (HFF-1) cells. A low cytotoxicity was observed for this nanoformulation starting at the highest concentrations used, namely, 400 and 800 μg. The hypoglycemic activity of insulin/ferrisilicate/PEG on acute administration in Wistar rats was studied using doses of 2, 5 and 10 mg/kg body weight. The developed facile ferrisilicate/PEG nanoformulation showed a high insulin encapsulation and loading capacity with pH-sensitive insulin release for potential delivery through the oral route.https://www.mdpi.com/1999-4923/15/2/593ferrisilicatePEGinsulinencapsulationdiabetic mellitus
spellingShingle B. Rabindran Jermy
Mohammed Salahuddin
Gazali Tanimu
Hatim Dafalla
Sarah Almofty
Vijaya Ravinayagam
Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus
Pharmaceutics
ferrisilicate
PEG
insulin
encapsulation
diabetic mellitus
title Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus
title_full Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus
title_fullStr Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus
title_full_unstemmed Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus
title_short Design and Evaluation of Pegylated Large 3D Pore Ferrisilicate as a Potential Insulin Protein Therapy to Treat Diabetic Mellitus
title_sort design and evaluation of pegylated large 3d pore ferrisilicate as a potential insulin protein therapy to treat diabetic mellitus
topic ferrisilicate
PEG
insulin
encapsulation
diabetic mellitus
url https://www.mdpi.com/1999-4923/15/2/593
work_keys_str_mv AT brabindranjermy designandevaluationofpegylatedlarge3dporeferrisilicateasapotentialinsulinproteintherapytotreatdiabeticmellitus
AT mohammedsalahuddin designandevaluationofpegylatedlarge3dporeferrisilicateasapotentialinsulinproteintherapytotreatdiabeticmellitus
AT gazalitanimu designandevaluationofpegylatedlarge3dporeferrisilicateasapotentialinsulinproteintherapytotreatdiabeticmellitus
AT hatimdafalla designandevaluationofpegylatedlarge3dporeferrisilicateasapotentialinsulinproteintherapytotreatdiabeticmellitus
AT sarahalmofty designandevaluationofpegylatedlarge3dporeferrisilicateasapotentialinsulinproteintherapytotreatdiabeticmellitus
AT vijayaravinayagam designandevaluationofpegylatedlarge3dporeferrisilicateasapotentialinsulinproteintherapytotreatdiabeticmellitus