An Update on Pharmacological Interventions for Diabetic Foot Ulcers

Abstract

Diabetic foot ulcers are the most common lower extremity complications of diabetes. Peripheral neuropathy and peripheral vascular disease are the underlying risk factors for diabetic foot ulcers, subsequently leading to infections and requiring antimicrobial therapy for the management of the disease. Each risk factor is a target for clinical intervention, with the intent to delay or prevent disease progression to amputation. The effective therapy includes interdisciplinary care, which involves optimized pharmacological interventions in concert with other treatments such as debridement strategies and specialized wound dressings. The pharmacological therapy alone cannot lead to successful therapy, and therefore, these supplementary techniques/modalities should not be overlooked. It is therefore the aim of this report to review various pharmacological interventions, specific to the diabetic foot and wound healing, along with incorporation of advanced therapies required to achieve a multifaceted treatment of diabetic foot ulcers and provide basis for superior drugs as well as drug delivery systems.

Topical Reformulation of Valsartan for Treatment of Chronic Diabetic Wounds

“…AT 1 R amplifies inflammatory signaling, a necessary activating function that leads to the proliferation phase but a function with potential negative consequences on wound healing in aging and diabetes as the inflammatory phase does Topical Valsartan for Diabetic Wound Healing not sufficiently resolve to allow proliferation and remodeling in granulation tissue. The blockade of the AT 1 R during the early stages of wound healing was associated with a slower closure rate, perhaps resulting from the disruption of the inflammatory phase and impairment of the transition to the proliferative and remodeling phases (Falanga, 2005;Pradhan et al, 2009;Scimeca et al, 2010;Stadelmann et al, 1998a;Van de Kerkhof et al, 1994). In previous reports, wounds in AT 1 R e/e mice had a delayed healing pattern when compared with controls (Yahata et al, 2006).…”

Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways

“…However, the beneficial effects of RAS blockade are quite confusing. In AT1R-knockout mice, wound healing was delayed relative to that in the controls 50 , perhaps resulting from the disruption of the inflammatory phase and the impairment of the transition to proliferation and remodeling 51 – 53 . The knockout of AT2R accelerated healing but impaird quality 54 .…”

Knockout of Angiotensin AT2 receptors accelerates healing but impairs quality

“…The lack of AT 2 R was associated with a slower closure rate during the early stages. This may have resulted from an unopposed pro-inflammatory AT 1 R, causing delayed resolution of the inflammatory phase and impairing the transition to the proliferative and remodeling phases [ 1 – 4 ; 35 ].…”

“…The biology of normal wound healing includes sequential yet overlapping inflammatory, proliferative, and remodeling phases that involve complex biological signaling [ 1 – 4 ]. Dysregulation of specific signaling pathways is thought to underlie skin breakdown and poor healing [ 1 – 4 ]. The renin angiotensin system (RAS) is active in connective tissue and skin, and is known to be important in wound healing [ 5 – 7 ].…”