Hydrogel formats to model potential drug interactions occurring at the subcutaneous injection site

Conor Gomes, Kate Gridley, Imogen Anastasiou, Bálint Sinkó, Randall J. Mrsny

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously developed an in vitro instrument, termed subcutaneous injection site simulator (SCISSOR), that can be used to monitor release properties of an active pharmaceutical ingredient (API) and formulation components of a medicine designed for SC injection. Initial studies to validate the SCISSOR instrument applications used a simple hyaluronic acid (HA) hydrogel to monitor early release events. We now report a type of cross-linked HA that can, when combined with HA, provide a hydrogel (HA-XR) with optical clarity and rheological properties that remain stable for at least 6 days. Incorporation of 0.05–0.1 mg/mL of collagens isolated from human fibroblasts (Col F), bovine type I collagen (Col I), chicken collagen type II (Col II), or chondroitin sulphate (CS) produced HA or HA-XR hydrogel formats with optical clarity and rheological properties comparable to HA or HA-XR alone. HA + Col F hydrogel had a much greater effect on release rates of 70 kDa compared to 4 kDa dextran, while Col F incorporated into the HA-XR hydrogel accentuated differences in release rates of prandial and basal forms of insulin as well as decreased the release rate of denosumab. A hydrogel format of HA + Col I was used to examine the complex events for bevacizumab release under conditions where a target ligand (vascular endothelial growth factor) can interact with extracellular matrix (ECM). Together, these data have demonstrated the feasibility of using a cross-linked HA format to examine API release over multiple days and incorporation of specific ECM elements to prepare more biomimetic hydrogels that allow for tractable examination of their potential impact of API release.

Original languageEnglish
Article number114308
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume199
Early online date28 Apr 2024
DOIs
Publication statusE-pub ahead of print - 28 Apr 2024

Data Availability Statement

Data will be made available on request.

Keywords

  • Drug fate
  • Extracellular matrix
  • In vitro model
  • Subcutaneous injection

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

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