Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study

Muhammet Emin Cam 1 2 3, Sila Yildiz 4, Hussain Alenezi 1 5, Sumeyye Cesur 2 6, Gul Sinemcan Ozcan 7, Gokce Erdemir 8, Ursula Edirisinghe 9, Dilek Akakin 7, Durdane Serap Kuruca 10, Levent Kabasakal 3, Oguzhan Gunduz 2 6, Mohan Edirisinghe 1

Affiliations

01 January 2020

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doi: 10.1098/rsif.2019.0712

Abstract

In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

Keywords: burst release; diabetic wound healing; drug delivery; fibres; pioglitazone; sustained release.

Conflict of interest statement

The authors have no competing interests.

Figures

Figure 1. The key physical properties of all solutions used in the experiments: (a) surface tension and (b) viscosity. (c) The production yield of all fibrous mat samples. (Online version in colour.)

Figure 1. The key physical properties of all solutions used in the experiments: (a) surface tension and (b) viscosity. (c) The production yield of all fibrous mat samples. (Online version in colour.)

Figure 2. SEM images of pure PVP fibrous mats and PHR-loaded PVP fibrous mats: (a) 10% (w/v) PVP, (b) 12% PVP, (c) 15% PVP, (d) 18% PVP, (e) 20% PVP, (f) PHR-loaded 12% PVP, (g) PHR-loaded 15% PVP, (h) PHR-loaded 18% PVP fibrous mats. SEM images of pure PVP/PCL (12%, w/v) fibrous mats and PHR-loaded PVP/PCL (12%, w/v) fibrous mats: (i) wPVP/wPCL = 8/2 PVP/PCL, (j) wPVP/wPCL = 7/3 PVP/PCL, (k) wPVP/wPCL = 6/4 PVP/PCL, (l) PHR-loaded (wPVP/wPCL = 6/4) PVP/PCL fibrous mats. show full caption

Figure 2. SEM images of pure PVP fibrous mats and PHR-loaded PVP fibrous mats: (a) 10% (w/v) PVP, (b) 12% PVP, (c) 15% PVP, (d) 18% PVP, (e) 20% PVP, (f) PHR-loaded 12% PVP, (g) PHR-loaded 15% PVP, (h) PHR-loaded 18% PVP fibrous mats. SEM images of pure PVP/PCL (12%, w/v) fibrous mats and PHR-loaded PVP/PCL (12%, w/v) fibrous mats: (i) wPVP/wPCL = 8/2 PVP/PCL, (j) wPVP/wPCL = 7/3 PVP/PCL, (k) wPVP/wPCL = 6/4 PVP/PCL, (l) PHR-loaded (wPVP/wPCL = 6/4) PVP/PCL fibrous mats. show full caption

Figure 3. FTIR spectra of pure PCL, pure PVP, pure PHR, PHR-loaded PVP fibrous mats at three different concentrations (12%, 15% and 18%), and PHR-loaded PVP/PCL fibrous mats. (Online version in colour.)

Figure 3. FTIR spectra of pure PCL, pure PVP, pure PHR, PHR-loaded PVP fibrous mats at three different concentrations (12%, 15% and 18%), and PHR-loaded PVP/PCL fibrous mats. (Online version in colour.)

Figure 4. XRD patterns of (a) PHR powder, (b) pure PVP, (c) PHR-loaded PVP (12%) fibrous mat, (d) PHR-loaded PVP (15%) fibrous mat, (e) PHR-loaded PVP (18%) fibrous mat, (f) pure PCL and (g) PHR-loaded PVP/PCL fibrous mat. (Online version in colour.)

Figure 4. XRD patterns of (a) PHR powder, (b) pure PVP, (c) PHR-loaded PVP (12%) fibrous mat, (d) PHR-loaded PVP (15%) fibrous mat, (e) PHR-loaded PVP (18%) fibrous mat, (f) pure PCL and (g) PHR-loaded PVP/PCL fibrous mat. (Online version in colour.)

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