Development and Evaluation of Alginate Membranes with Curcumin-Loaded Nanoparticles for Potential Wound-Healing Applications

Abstract

Non-biodegradable materials with a low swelling capacity and which are opaque and occlusive are the main problems associated with the clinical performance of some commercially available wound dressings. In this work, a novel biodegradable wound dressing was developed by means of alginate membrane and polycaprolactone nanoparticles loaded with curcumin for potential use in wound healing. Curcumin was employed as a model drug due to its important properties in wound healing, including antimicrobial, antifungal, and anti-inflammatory effects. To determine the potential use of wound dressing, in vitro, ex vivo, and in vivo studies were carried out. The novel membrane exhibited the diverse functional characteristics required to perform as a substitute for synthetic skin, such as a high capacity for swelling and adherence to the skin, evidence of pores to regulate the loss of transepidermal water, transparency for monitoring the wound, and drug-controlled release by the incorporation of nanoparticles. The incorporation of the nanocarriers aids the drug in permeating into different skin layers, solving the solubility problems of curcumin. The clinical application of this system would cover extensive areas of mixed first- and second-degree wounds, without the need for removal, thus decreasing the patient's discomfort and the risk of altering the formation of the new epithelium.

Keywords: Franz cells; alginate; curcumin; drug skin permeation; nanoparticles; pluronic F68; polymeric membrane; tape stripping; wound dressing.

Figure 1

Atomic force microscopy (AFM) topography images of the CNp. The size bar is 1 µm.

Figure 2

Percentage of swelling in alginate membranes as a function of time. Effect on swelling capacity by the addition of PVA + glycerin (M1), PVA + glycerin + propylene glycol (M2), PVP + glycerin (M3), PVP + glycerin + propylene glycol (M4), and CNp + PVP + glycerin + propylene glycol (CNp‒M4) (mean ± SE; n = 3). There were significant differences when ANOVA was applied at 5, 20, 30, and 60 min (p < 0.05).

Figure 3

Effect of plasticizers on the mechanical properties of alginate membranes. Effect on mechanical properties by the addition of PVA + glycerin (M1), PVA + glycerin + propylene glycol (M2), PVP + glycerin (M3), PVP + glycerin + propylene glycol (M4), and CNp + PVP + glycerin + propylene glycol (CNp‒M4), respectively. (a) Elongation at break; (b) tensile stress, (mean ± SD; n = 3). * indicates p < 0.05 as statistically significant.

Figure 4

Thermal analysis of nanoparticle-coated alginate membrane using (a) thermogravimetric analysis (TGA) and (b) differential scanning calorimetry (DSC). The thermal properties of the M4 membrane, CNp‒M4 membrane, CNp, and curcumin are represented as a, b, c, and d, respectively.

Figure 5

Morphology and porosity of alginate membranes. (a) Micrographs by scanning electronic microscopy of the alginate membrane surface (A, B, D, and E) and membrane thickness (C and F). Magnification of 100× for A, D; 220× in B, C, E and F; the scale bar is 100 μm; (b) pore diameter and membrane thickness of M4 and CNp‒M4 membranes, mean ± SE, n = 3. * indicates that p < 0.05 is statistically significant.

Figure 6

Alginate membranes (M4) before swelling and during the swelling process in PBS medium (A,B, respectively), and alginate membranes with curcumin nanoparticles (CNp‒M4) before swelling and during the swelling process in PBS medium (C,D, respectively). Scale in centimeters.

Figure 7

Release profile of curcumin from the drug dispersion, CNp and CNp‒M4 membrane in PBS pH 7.4 (0.1 M, Pluronic^® F-127 2% w/v) at 37 °C. Each point represents the mean ± SE, n = 3.

Figure 8

Ex vivo permeation of curcumin after 30 h of treatment with drug dispersion, CNp dispersion, or CNp‒M4 membrane. Stratum corneum-bound particles (obtained from 15 tape strips), epidermis + dermis (surface on which dosed skin was handled after 30 h), and systemic (receptor compartment), mean ± SE, n = 4; ** indicates p < 0.01 and *** indicates p < 0.001 as statistically significant.

Figure 9

Cumulative concentration of curcumin quantified in the stratum corneum of healthy volunteers. Drug extraction from 15 adhesive tapes applied to the treatment site after placing a CNp‒M4 membrane, CNp dispersion, or drug dispersion for 6 h (mean ± SE; n = 4).