Impact of ZIF-8, ArgHCl, and Ionic Liquid-Based Formulations on the Conformational and Colloidal Stability of Antibodies

Mol Pharm. 2023 Jun 5;20(6):3150-3159. doi: 10.1021/acs.molpharmaceut.3c00167. Epub 2023 May 10.

Abstract

Various formulations consisting of biomaterials zirconium imidazolate framework-8 (ZIF-8), choline acetate ([Ch][Ac]), and arginine hydrochloride (argHCl) are optimized to study the stability of antibody, Immunoglobulin G (IgG). We have performed several instrumentations including UV-visible spectroscopy, dynamic light scattering (DLS), circular dichroism (far UV CD), and atomic force microscopy (AFM) in the presence of all the formulations to investigate the conformational and colloidal stability of the antibodies. Alongside, the packing efficiency of all the formulations was also explored by storing IgG at 4 °C for 3 months. We have tried to investigate the interactions between biomaterials and antibodies with the motive of designing aggregation-resistant formulations. The overall stability of IgG was improved in the presence of [Ch][Ac]; however, ZIF-8 and argHCl cause relatively more aggregation, although the structure was retained in all the formulations. The key aspect of this study is that the presence of [Ch][Ac] increases ZIF-8@IgG's thermal stability and resistance to IgG-argHCl aggregation. All over, for the first time, with different experimental approaches, the impact of each biomaterial individually and in combination is explored to study their effect on the stability of antibodies. Thus, better efficient formulations can be designed for the storage/packaging of IgG-based drugs which ultimately will have more applicability in pharmaceuticals.

Keywords: ZIF-8; antibody aggregation; argHCl; choline acetate; conformational and colloidal stabilities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Compounding
  • Immunoglobulin G / chemistry
  • Ionic Liquids*
  • Protein Conformation
  • Protein Stability
  • Zirconium

Substances

  • Ionic Liquids
  • Zirconium
  • Immunoglobulin G