Journal
PHARMACEUTICS
Volume 12, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics12040334
Keywords
epidermal growth factor (EGF); coacervate; alginate; gelatin; diabetic foot ulcer; drug delivery system; epidermal migration; proinflammatory cytokines
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Funding
- National Research Foundation of Korea [NRF-2017R1D1A1B03031548]
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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-alpha. Freeze-dried coacervates packaged in aluminum pouches were stable for up to 4 months at 4 and 25 degrees 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 degrees 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.
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