Peptide-loaded, shear sensitive hydrogel as a novel topical delivery system for wound management and repair

Abstract

The use of pharmaceutically active peptides and proteins has increased significantly over the last 30 years. Topical delivery of growth factors to chronic wounds to enhance wound management and repair have been of particular interest. The aim of the work in this thesis was to evaluate the ability of the PVA-borate hydrogel formulation to deliver biologically active protein payloads. The unique viscoelastic properties of PVA-borate hydrogels are advantageous for application to wounds.
The hydrogel can flow into the wound crevasses providing maximal surface area for drug delivery. Yet, they maintain enough cohesive integrity of its cross-linked network to allow for complete and intact removal from the wound, without causing any trauma to newly formed tissue. The ability of the PVA-borate hydrogel to maintain a moist environment and also absorb small volumes of exudate from low exuding wounds also aids wound healing.
Several model payloads (BSA, haemoglobin, trypsin and pepsin) were
incorporated into the hydrogel. These proteins where found to change the
viscoelastic properties of the PVA-borate hydrogel, but, were released in a sustained manner from the hydrogel without undergoing any degradation. This investigation indicated that the PVA-borate hydrogel is capable of providing a sustained release of protein payloads with certain physical and chemical characteristics.
Insulin-like growth factor-1 (IGF-1) was incorporated into the hydrogel and
found not to effect the viscoelastic properties of the hydrogel. In vitro release studies confirmed that the hydrogel provided a sustained release of IGF-1, which had maintained its biological activity and not experienced any degradation.
Cell culture studies confirmed that IGF-1-loaded PVA-borate hydrogels can
stimulate fibroblast and keratinocyte migration and proliferation. Therefore, the
iv work in this thesis demonstrates that IGF-1-loaded hydrogels may have a beneficial use in the management and repair of chronic and recalcitrant wounds.

Date of Award	May 2018
Original language	English
Sponsors	Department of Employment and Learning
Supervisor	Paul Mc Carron (Supervisor), Nigel Ternan (Supervisor) & Murtaza M Tambuwala (Supervisor)