PEGylated Substance P Augments Therapeutic Angiogenesis in Diabetic Critical Limb Ischemia

Publication date: Available online 29 May 2019Source: Journal of Industrial and Engineering ChemistryAuthor(s): Hyun-Ji Park, Suna Kim, Eun Je Jeon, In-Taek Song, Haeshin Lee, Youngsook Son, Hyun Sook Hong, Seung-Woo ChoAbstractSubstance P (SP) is a therapeutic peptide that has been widely used to induce angiogenesis and tissue regeneration. However, its therapeutic efficacy is often limited due to rapid degradation in vivo and a short half-life (˜1 min) after systemic administration. In the present study, we chemically modified SP with polyethylene glycol (PEG) to generate long-lasting formulations with increased stability and extended retention time in vivo and evaluated their ability to enhance therapeutic angiogenesis. Compared to the unmodified SP, PEGylated SP (PEG-SP) exhibited significantly increased half-life in vivo (˜360-fold increase in normal mouse and ˜120-fold increase in diabetic mouse). Systemic injection of PEG-SP led to a marked increase in therapeutic efficacy and angiogenesis in diabetic hindlimb ischemia, as evident from the remarkable improvement in salvage of ischemic limb and recovery of blood perfusion in diabetic mice with limb ischemia. These formulations increased endogenous stem cell mobilization to the injured site and modulated the immune system to increase microvessel formation and reduce systemic inflammation. Importantly, PEGylation efficiently reduced the injection doses of SP while still maintaining its therapeutic efficacy. To conclu...
Source: Journal of Industrial and Engineering Chemistry - Category: Chemistry Source Type: research