Deferoxamine-loaded transfersomes accelerates healing of pressure ulcers in streptozotocin-induced diabetic rats

Diabetic nonhealing ulcers are the leading cause of nontraumatic amputations. An increased cancer risk has been found in patients treated with current therapies such as becaplermin gel. Therefore, an urgent need exists for novel approaches to control delayed ulcer healing. HIF-1α mediates adaptive responses to hypoxia by regulating angiogenesis, proliferation, migration, and cell survival. However, its function is impaired by hyperglycemia. Deferoxamine (DFO) might be an effective HIF-1α stabilizer by inhibiting PHD enzyme through the prevention of iron release in diabetic tissue. Herein, transfersomes were used as nanocarriers for DFO. The system depends on the ability of transfersomes to enhance the penetration of the large hydrophilic drug, DFO through the skin and sustain its release by applying a two-factor, three-level full factorial design to optimize entrapment efficiency, particle size, zeta potential and in vitro drug release. The soybean phosphatidylcholine (SPC) amount and the ratio of surfactant to SPC were selected as independent variables. The formulations had an entrapment efficiency range of 54.46–91.56%, particle size range of 109.2–265.6 nm, polydispersity index values less than one and negative zeta potential range of −17.53 to −29.03 mV. In vitro study revealed that the DFO-loaded transfersomal gel has uniform distribution of DFO, applicable pH, and suitable viscosity and found effective in sustaining DFO release. Moreover, in-vivo study of the optimized formulation demonstrated cutaneous wound healing potential in rats’ diabetic pressure ulcers. Overall, DFO-loaded transfersomal gel shows promise as a potential therapy for the treatment of human diabetic ulcers. • Transfersomal gel significantly augmented sustained delivery of DFO. • DFO transfersomal gel effected carrying hydrophilic DFO into deeper layers of skin. • DFO transfersomal gel increased the rate of neovascularization. • DFO transfersomal gel increased the production of collagen fibers. • DFO transfersomal gel led to a marked acceleration of ulcer healing process.