Improved Diabetic Wound Healing by EGF Encapsulation in Gelatin-Alginate Coacervates

• Published in: Pharmaceutics Vol. 12; no. 4; p. 334
• Main Authors: Jeong, Seonghee, Kim, ByungWook, Park, Minwoo, Ban, Eunmi, Lee, Soo-Hyeon, Kim, Aeri
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.04.2020; MDPI
• Subjects: Acids; alginate; Biomedical materials; Diabetes; diabetic foot ulcer; drug delivery system; Epidermal growth factor; epidermal growth factor (EGF), coacervate; epidermal migration; Experiments; Foot diseases; gelatin; Leg ulcers; Molecular weight; Wound healing; United States > US; South Korea; Germany; alginate; proinflammatory cytokines; epidermal migration; diabetic foot ulcer; drug delivery system; epidermal growth factor (EGF), coacervate; gelatin
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics12040334

Topical imageplication of epidermal growth fctor (EGF) has been used to accelerate diabetic foot ulcers but with limited efficacy. In this study, we selected a complex coacervate (EGF-Coa) composed of the low molecular weight gelatin type A and sodium alginate as a novel delivery system for EGF, based on encapsulation efficiency and protection of EGF from protease. EGF-Coa enhanced in vitro migration of keratinocytes and accelerated wound healing in streptozotocin-induced diabetic mice with increased granulation and re-epithelialization. While diabetic wound sites without treatment showed downward growth of hyperproliferative epidermis along the wound edges with poor matrix formation, EGF-Coa treatment recovered horizontal migration of epidermis over the newly deposited dermal matrix. EGF-Coa treatment also resulted in reduced levels of proinflammatory cytokines IL-1, IL-6, and THF-α. Freeze-dried coacervates packaged in aluminum pouches were stable for up to 4 months at 4 and 25 °C in terms of appearance, purity by RP-HPLC, and in vitro release profiles. There were significant physical and chemical changes in relative humidity above 33% or at 37 °C, suggesting the requirement for moisture-proof packaging and cold chain storage for long term stability. We propose low molecular weight gelatin type A and sodium alginate (LWGA-SA) coacervates as a novel EGF delivery system with enhanced efficacy for chronic wounds.