Wound Healing Composite Materials of Bacterial Cellulose and Zinc Oxide Nanoparticles with Immobilized Betulin Diphosphate

Abstract

A design of new nanocomposites of bacterial cellulose (BC) and betulin diphosphate (BDP) pre-impregnated into the surface of zinc oxide nanoparticles (ZnO NPs) for the production of wound dressings is proposed. The sizes of crystalline BC and ZnO NPs (5-25%) corresponded to 5-6 nm and 10-18 nm, respectively (powder X-ray diffractometry (PXRD), Fourier-infrared (FTIR), ultraviolet (UV), atomic absorption (AAS) and photoluminescence (PL) spectroscopies). The biological activity of the wound dressings "BC-ZnO NPs-BDP" was investigated in rats using a burn wound model. Morpho-histological studies have shown that more intensive healing was observed during treatment with hydrophilic nanocomposites than the oleophilic standard (ZnO NPs-BDP oleogel; p < 0.001). Treatment by both hydrophilic and lipophilic agents led to increases in antioxidant enzyme activity (superoxide dismutase (SOD), catalase) in erythrocytes and decreases in the malondialdehyde (MDA) concentration by 7, 10 and 21 days (p < 0.001). The microcirculation index was restored on the 3rd day after burn under treatment with BC-ZnO NPs-BDP wound dressings. The results of effective wound healing with BC-ZnO NPs-BDP nanocomposites can be explained by the synergistic effect of all nanocomposite components, which regulate oxygenation and microcirculation, reducing hypoxia and oxidative stress in a burn wound.

Keywords: antioxidant properties; bacterial cellulose; betulin diphosphate; burns; wound dressings; zinc oxide nanoparticles.

Figure 5

The dependence of BDP microspecies distributions (%) on pH calculated using Chemicalize program [54].

Figure 1

Powder XRD patterns of BC-ZnO samples: (a) ZnO NPs-PEG, (b) BC powder, (c) BC film–ZnO NPs, and (d) BC powder–ZnO NPs.

Figure 2

Powder XRD patterns of compositions (BC 0.5 g + ZnO NPs 0.15 g) samples, formed in different conditions in the presence of tris (a) or DDS-Na (b).

Figure 3

Powder XRD patterns of compositions (BC-ZnO NPs) samples, with concentrations of ZnO NPs: a). 6.6%; b). 16.9%; c). 26%.

Figure 4

Powder XRD patterns of BC compositions: (a). BC-BDP (1%); (b). BC (DDS-Na 0.01%) + ZnO NPs+ BDP.

Figure 6

Schematic representation of the formation of negative charge.

Figure 7

Scanning electron microscopy (SEM) images of ZnO NPs (a) and ZnO NPs modified by BDP (b), ×30,000.

Figure 8

Formulas of betulin-3,28-diphosphate (BDP) and cellulose unit.

Figure 9

SEM images: BC hydrogel film ×30 (a) and ×150 (b); BC-ZnO NPs-BDP hydrogel film ×500 (c) and ×1200 (d).

Figure 10

The assay of zinc ions released from BC-ZnO NPs-BDP nanocomposite films as membrane in water as a function of time using Franz vertical diffusion cells.

Figure 11

The burn wound state on day 21 after treatment.

Figure 12

Diagram of changes in MDA concentration in plasma and blood erythrocytes (μmol/L) during treatment with the studied drugs (% of control). Number of experiment replications was equal to 3. p < 0.001. MDA pl (a) and MDA er (b) mean the level of MDA in blood plasma and erythrocytes.

Figure 13

Diagram of changes in superoxide dismutase (SOD) activity during treatment with the studied agents (% of control), 100%—1037.762 ± 21.351% ng min⁻¹ mg protein⁻¹. The number of experiment replications was equal to 3. p < 0.001.