rhEGF-loaded PLGA-Alginate microspheres enhance the healing of full-thickness excisional wounds in diabetised Wistar rats

Abstract

Diabetic foot ulcers (DFUs) represent a major clinical challenge in the ageing population. To address this problem, rhEGF-loaded Poly-Lactic-co-Glycolic-Acid (PLGA)-Alginate microspheres (MS) were prepared by a modified w/o/w-doubleemulsion/solvent evaporation method. Different formulations were evaluated with the aim of optimising MSs properties by adding NaCl to the surfactant solution and/or the solvent removal phase and adding alginate as a second polymer. The characterization of the developed MS showed that alginate incorporation increased the encapsulation efficiency (EE) and NaCl besides increasing the EE also became the particle surface smooth and regular. Once the MS were optimised, the target loading of rhEGF was increased to 1% (PLGA-Alginate MS), and particles were sterilised by gamma radiation to provide the correct dosage for in vivo studies. In vitro cell culture assays demonstrated that neither the microencapsulation nor the sterilisation process affected rhEGF bioactivity or rhEGF wound contraction. Finally, the MS were evaluated in vivo for treatment of the full-thickness wound model in diabetised Wistar rats. rhEGF MS treated animals showed a statistically significant decrease of the wound area by days 7 and 11, a complete re-epithelisation by day 11 and an earlier resolution of the inflammatory process. Overall, these findings demonstrate the promising potential of rhEGF-loaded MS (PLGA-Alginate MS) to promote faster and more effective wound healing, and suggest its possible application in DFU treatment.

Recent developments in novel drug delivery systems for wound healing

“…Such dressings can provide several advantages over the conventional dressings. It improved patient compliance, enhanced safety of the drugs, reduced the need for frequent dressing change, delivered wound healing drugs directly to wound sites, release the drug in a sustained fashion over a prolonged periods of time and show superior wound healing activity in vivo [20,24]. Different formulation approaches that have been successfully demonstrated include nano and microparticles, microemulsions, SLNs, sponges, liposomes, films and mats.…”

“…The in vivo effect of rhEGF containing microspheres was also significantly greater (p < 0.005) than that of the pure rhEGF on the diabetic ulcers model in rats by prolonging its effective time and ultimately improves its therapeutic efficacy. In another study by Gainza et al [20], rhEGF was loaded into PLGA-Alginate microspheres and evaluated for its effectiveness in healing full thickness wounds inflicted on 1 week diabetic rats. In terms of wound contraction, epidermal regeneration and inflammatory stage recovery, rhEGF-loaded PLGA-Alginate microspheres demonstrate promising potential in promoting faster and more effective wound healing.…”

Controlled Release of Thymosin Beta 4 Using a Collagen–Chitosan Sponge Scaffold Augments Cutaneous Wound Healing and Increases Angiogenesis in Diabetic Rats with Hindlimb Ischemia

“…rhEGF-loaded PLGA-Alginate microspheres promote faster diabetic wound healing, in terms of epidermal regeneration and inflammation inhibition. 7 However, the etiology of diabetic chronic cutaneous wounds is complex and multifaceted and these efforts have not been able to meet the expectations of guaranteed, adequate wound healing.…”

Do Mesenchymal Stem Cells Have a Role to Play in Cutaneous Wound Healing?

“…62 Several other constructs including the recombinant human EGF-loaded poly-lacticco-glycolic-acid-alginate microspheres, fibrin-based scaffold incorporating VEGF-and Basic Fibroblast Growth Factor (bFGF)-loaded nanoparticles, PDGF on gelatin gel and recombinant human granulocyte/macrophage colony-stimulating factor hydrogel have all found capable of accelerating the wound healing response. [63][64][65][66] Tissue engineering with the use of genetically modified cells expressing several growth factors have been analyzed as an alternative to the above mentioned approaches. Yan et al in a porcine model of radiation-induced skin injury analyzed the effect of topical transplantation of constructs composed of acellular human amniotic membrane together with autologous BM-MSCs and skin-derived keratinocytes infected by recombinant retrovirus expressing human PDGF-A.…”