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

B. Rabindran Jermy*, Mohammed Salahuddin, Gazali Tanimu, Hatim Dafalla, Sarah Almofty, Vijaya Ravinayagam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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. Fe3+ species were identified using diffuse reflectance spectroscopy. The large surface area (804 m2/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.

Original languageEnglish
Article number593
JournalPharmaceutics
Volume15
Issue number2
DOIs
StatePublished - Feb 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • PEG
  • diabetic mellitus
  • encapsulation
  • ferrisilicate
  • insulin

ASJC Scopus subject areas

  • Pharmaceutical Science

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