Co-delivery of deferoxamine and hydroxysafflor yellow A to accelerate diabetic wound healing via enhanced angiogenesis

Abstract

Nonhealing chronic wounds on foot induced by diabetes is a complicated pathologic process. They are mainly caused by impaired neovascularization, neuropathy, and excessive inflammation. A strategy, which can accelerate the vessel network formation as well as inhibit inflammatory response at the same time, makes it possible for effective diabetic ulcers treatment. Co-delivery of multiple drugs with complementary bioactivity offers a strategy to properly treat diabetic wound. We previously demonstrated that hydroxysafflor yellow A (HSYA) could accelerate diabetic wound healing through promoting angiogenesis and reducing inflammatory response. In order to further enhance blood vessel formation, a pro-angiogenic molecular called deferoxamine (DFO) was topically co-administrated with HSYA. The in vitro results showed that the combination of DFO and HSYA exerted synergistic effect on enhancing angiogenesis by upregulation of hypoxia inducible factor-1 alpha (HIF-1α) expression. The interpenetrating polymer networks hydrogels, characterized by good breathability and water absorption, were designed for co-loading of DFO and HSYA aiming to recruit angiogenesis relative cells and upgrade wound healing in vivo. Both DFO and HSYA in hydrogel have achieved sustained release. The in vivo studies indicated that HSYA/DFO hydrogel could accelerate diabetic wound healing. With a high expression of Hif-1α which is similar to that of normal tissue. The noninvasive US/PA imaging revealed that the wound could be recovered completely with abundant blood perfusion in dermis after given HSYA/DFO hydrogel for 28 days. In conclusion, combination of pro-angiogenic small molecule DFO and HSYA in hydrogel provides a promising strategy to productively promote diabetic wound healing as well as better the repair quality.

Hydroxysafflor Yellow A: A Systematical Review on Botanical Resources, Physicochemical Properties, Drug Delivery System, Pharmacokinetics, and Pharmacological Effects

“…The combination of HSYA and deferoxamine (DFO) was discovered to improve type 1 diabetes by accelerating diabetic wound healing, promoting angiogenesis, reducing the inflammatory response, and up-regulating the expression of hypoxia-inducible factor-1 a (HIF-1 α) ( Gao et al, 2018 ).…”

Pharmacokinetics of Active Ingredients of Salvia miltiorrhiza and Carthamus tinctorius in Compatibility in Normal and Cerebral Ischemia Rats: A Comparative Study

“…It is often used for the treatment of cardio-cerebral-vascular disease caused by blood stasis [30,44,45]. Existing studies have shown that DSS, SAA, SAB, and HSYA have the ability to scavenge free oxygen radicals, inhibit apoptosis, and prevent inflammation [5][6][7][8][9][10][11][12][13][14][15][16][17][18][25][26][27][28], thereby protecting against cerebral ischemic injury. Over the past few years, the Dan-Hong injection and its ingredients have been widely studied in clinical and basic research [30,[46][47][48].…”

“…DSS is an important water-soluble ingredient, which has been pharmacologically shown to improve blood circulation [19] and eliminate blood stasis [20,21], and can also protect against cerebral ischemia reperfusion injury [22]. HSYA can inhibit platelet aggregation [23,24], reduce inflammatory response [25][26][27][28] and protect against myocardial ischemia [29,30].…”

Bioactive Molecules for Skin Repair and Regeneration: Progress and Perspectives

“…Hydroxysafflor yellow A and deferoxamine have been reported to accelerate wound healing through promoting angiogenesis and reducing the inflammatory. And the deferoxamine and hydroxysafflor yellow A hydrogel could accelerate diabetic wound healing via enhanced angiogenesis by upregulation of hypoxia-inducible factor-1 alpha expression [103]. AES16-2M, an extracellular signal-regulated kinase-activating peptide, activated the MAPK signaling pathway and promoted wound healing through accelerating the migration of keratinocytes [104].…”