<p>Sesamol-Loaded PLGA Nanosuspension for Accelerating Wound Healing in Diabetic Foot Ulcer in Rats</p>

Abstract

Background: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, antihyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition. Methods: Sesamol-PLGA (SM-PLGA) nanosuspension was developed using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound reepithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson's trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections. Results: The optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels' development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed. Conclusion: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.

Clinical Study on the Efficacy of Silver Ion Dressing Combined with Prontosan Gel Dressing in the Treatment of Diabetic Foot Ulcers and the Effect on Serum Inflammatory Factors

“…The combination of local infection is a major risk factor for recovery from diabetic foot disease. Local inflammatory response is a protective response to a noxious stimulus, but excessive inflammation can exacerbate the damage, and it has been shown that high levels of inflammatory factors are closely associated with the persistence of DFU [ 17 , 18 ]. The current treatment of DFU includes glycemic control, improvement of microcirculation, improvement of neurological function, topical dressing of the trauma, and revascularisation [ 19 ].…”

Sesamol Attenuates Neuroinflammation by Regulating the AMPK/SIRT1/NF-κB Signaling Pathway after Spinal Cord Injury in Mice

“…Sesamol is extracted from sesame oil and can be used as an antioxidant in foods and medicines [ 44 ]. Several studies have revealed that sesamol protects the body from various disease conditions such as obesity, hyperlipidemia, and diabetic foot ulcer mainly through regulating lipid as well as energy metabolism and reducing inflammatory cell infiltration [ 45 – 47 ]. Ample previous studies have also documented that sesamol has anti-inflammatory effects via upregulating AMPK signaling and inhibiting NF- κ B activation [ 26 , 27 ].…”

An Insight Into Sesamol: Pharmacological Activities, and Future Research Prospects

“…BCL-2 and stimulation of bax (BCL2 Associated X, Apoptosis Regulator) (BAX BCL2 Associated X, Apoptosis Regulator is a Protein coding gene. Protein expression on treatment with both free and encapsulated sesamol was responsible for the induction of apoptosis in tumor cells [43].…”