Fabrication and Characterization of Phyllanthus Emblica Extract-Polyvinyl Alcohol/Carboxymethyl Cellulose Sodium Antioxidant Hydrogel and Its Application in Wound Healing

Abstract

Background: Phyllanthus emblica is a medicinal and edible plant from the Euphorbiaceae family, notable for its rich content of polyphenols and flavonoids, which provide significant antioxidant properties. To exploit the full antioxidant potential of Phyllanthus emblica, this study developed a hydrogel system incorporating polyvinyl alcohol (PVA) and carboxymethyl cellulose sodium (CMC-Na), integrated with Phyllanthus emblica extract, for the purpose of wound healing. Methods: The extraction process of active ingredients of Phyllanthus emblica was optimized and assessed the antioxidant composition and activity of the extract. A series of hydrogel performance evaluations were performed on the Phyllanthus emblica extract-loaded PVA/CMC-Na hydrogel (AEPE composite hydrogel). Additionally, the wound healing efficacy was evaluated through cell culture experiments and wound healing assays using BALB/C mice. Results: The findings indicated that the extraction of Phyllanthus emblica with 95% ethanol yielded an extract rich in polyphenols, primarily gallic acid and ellagic acid, demonstrating high free radical scavenging capacity and robust antioxidant activity. The hydrogel matrix containing 12% PVA and 1% CMC-Na exhibited excellent physicochemical properties. The optimized AEPE composite hydrogel enabled sustained drug release over a 24 h period, exhibited low cytotoxicity and promoted cell migration. In a mouse dorsal wound healing model, the AEPE composite hydrogel showed pronounced anti-inflammatory and antioxidation effects, enhanced collagen deposition, and ultimately accelerated wound healing. Conclusions: The AEPE composite hydrogel demonstrated strong antioxidant characteristics and significant wound healing potential. Thus, this study could broaden the application prospects of Phyllanthus emblica in wound healing.

Keywords: PVA/CMC-Na hydrogel; Phyllanthus emblica; anti-inflammatory; antioxidant; gallic acid; polyphenol; sustained release; wound healing.

Figure 1

(a) Contents of total polyphenols in water extract (WEPE) and ethanol extract (AEPE) of Phyllanthus emblica; (b) scavenging rate of DPPH, ABTS⁺, and hydroxyl radical by Phyllanthus emblica officinalis extracts; HPLC of gallic acid (c), ellagic acid (d), and AEPE (e). # represents the difference between each solvent extraction and gallic acid (# p < 0.05, ### p < 0.001); * represents the difference between individual solvent extracts (mean ± SD, n = 3; * p < 0.05, *** p < 0.001).

Figure 2

Evaluation of AEPE composite hydrogel performance: (a) residual weight rate of hydrogel with different ratios at 24 h and (b) 72 h; (c) maximum swelling rate of hydrogel with different ratios; (d) water retention of hydrogel with different ratios; (e) wetting rate of hydrogel with different ratios; (f) hydrogel fraction of hydrogel with different ratios. # represents the difference between CMC-Na with each content and 0% CMC-Na (# p < 0.05, ## p < 0.01, ### p < 0.001); * represents the difference between the CMC-Na of each content (mean ± SD, n = 3; * p < 0.05, ** p < 0.01).

Figure 3

Scanning electron microscopy images of (a) PVA/CMC-Na hydrogel and (b) AEPE composite hydrogel (** p < 0.01, *** p < 0.001); (c) free radical scavenging of the AEPE composite hydrogel; (d) in vitro release curves of PVA/CMC-Na hydrogel with different gallic acid contents over 24 h. Rheological tests: (e) shear viscosity and (f) frequency scanning.

Figure 4

(a) Cell viabilities of 3T6-Swiss albino mice treated with free film for 24 h and 48 h; (b) rates and (c) fibroblast migration behaviors after blank hydrogel with AEPE hydrogel. # represents the difference between hydrogel of each group and control group (### p < 0.001); * represents the difference between the hydrogels of each group (mean ± SD, n = 3; ** p < 0.01, *** p < 0.001).

Figure 5

(a) The wound healing processes recorded for the rats by using different treatments (control, AEPE, blank hydrogel, and AEPE hydrogel) at various times (0–14 days); (b) time-dependent wound healing area after different treatments. (c) Histological analysis of tumor sections on day 14 after different treatments. (d) TNF-α, IL-1β, and IL-6 concentrations, expressed as pg/mL, in the control and treatment groups (d7). # represents the difference between the treatment groups and the control group (### p < 0.001); * represents the difference between treatment groups (mean ± SD, n = 3; * p < 0.05, ** p < 0.01, *** p < 0.001).