Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing

Abstract

Hydrogels provide effective alternatives for drug delivery when therapeutics cannot be applied directly to a wound, or if adverse effects are associated with systemic administration. However, drug delivery vehicles need to be biocompatible and biodegradable and exhibit sufficient mechanical strength to withstand handling and different physiological conditions, such as those encountered during topical administration of a therapeutic. Wound healing can be divided into three phases stimulated by transforming growth factor-beta (TGF-β) and, subsequently, targeted therapeutics have been developed to inhibit this cytokine for the treatment of chronic wounds and to prevent scarring. In this study, the capacity of calcium alginate hydrogels plasticized with poly(ethylene glycol) methyl ether methacrylate (PEGMA) to deliver anti-TGF-β antibodies (1D11.16.8) to a wound was investigated in situ. Three levels of antibodies, 10, 50, and 100 μg, were loaded into calcium-alginate-PEGMA hydrogels and evaluated in an excisional wound model in mice. Hydrogels containing 50 and 100 μg 1D11.16.8 produced less inflammation, accompanied by a marked reduction in collagen deposition and cell infiltration. These findings demonstrate the capacity of calcium-alginate-PEGMA hydrogels to deliver larger proteins, such as antibodies, to the site of a wound.

Keywords

• hydrogel
• wound healing
• Ca-alginate
• poly(ethylene glycol) methyl ether methacrylate
• 1D11
• TGF-β