Fabrication, In Vitro, and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing

Abstract

Wounds are the most common causes of mortality all over the world. Topical drug delivery systems are more efficient in treating wounds as compared to oral delivery systems because they bypass the disadvantages of the oral route. The aim of the present study was to formulate and evaluate in vitro in vivo nanoemulgels loaded with eucalyptol for wound healing. Nanoemulsions were prepared using the solvent emulsification diffusion method by mixing an aqueous phase and an oil phase, and a nanoemulgel was then fabricated by mixing nanoemulsions with a gelling agent (Carbopol 940) in a 1:1 ratio. The nanoemulgels were evaluated regarding stability, homogeneity, pH, viscosity, Fourier-transform infrared spectroscopy (FTIR), droplet size, zeta potential, polydispersity index (PDI), spreadability, drug content, in vitro drug release, and in vivo study. The optimized formulation, F5, exhibited pH values between 5 and 6, with no significant variations at different temperatures, and acceptable homogeneity and spreadability. F5 had a droplet size of 139 ± 5.8 nm, with a low polydispersity index. FTIR studies showed the compatibility of the drug with the excipients. The drug content of F5 was 94.81%. The percentage of wound contraction of the experimental, standard, and control groups were 100% ± 0.015, 98.170% ± 0.749, and 70.846% ± 0.830, respectively. Statistically, the experimental group showed a significant difference (p < 0.03) from the other two groups. The results suggest that the formulated optimized dosage showed optimum stability, and it can be considered an effective wound healing alternative.

Status and Future Scope of Soft Nanoparticles-Based Hydrogel in Wound Healing

“…Classical emulsions are characterized by a coarse droplet size that can reach 1 μm. In comparison to conventional emulsions, the nanosized droplets are more kinetically stable, resulting in a lower tendency to creaming, sedimentation, flocculation, or coalescence [ 87 , 88 ]. Likewise, NE is composed of immiscible liquids that formed a single phase by an emulsifier and can be prepared by using materials from natural sources, such as essential oils and herbal-based compounds [ 97 , 98 ].…”

“…In contrast, chitosan hydrogels containing phenytoin associated with NE or NC showed particles in the micrometric range (>1 mm), probably due to the nanoparticle aggregation in the polymer network [ 71 , 100 ]. Eucalyptol NE also presented an increase in mean droplet size when converted into a Carbopol ® nanoemulgel (112 ± 0.77 and 139 ± 5.8 mm for NE and nanoemulgel, respectively) [ 87 ].…”

“…Plant-derived essential oils and their bioactive compounds present pharmacological properties that are relevant for the wound healing process, such as antifungal, antibacterial, antioxidant, and anti-inflammatory [ 87 , 106 ]. Eucalyptol (EU) is the most important component of Eucalyptus and could improve the wound-healing process by enhancing the capillary permeability after its administration via the intradermal route.…”

“…The optimized formulation had a healing rate similar to the commercial product (Quench ® cream containing silver sulphadiazine), reaching 100% of wound contraction after 15 days. Such an effect was attributed to the increased contact time with the skin provided by the nanocarriers, which enhances EU permeability and the final pharmacological effect [ 87 ].…”

“…p < 0.02 and p < 0.04 refer to the statistical significance of both groups from the control. Data are available at 10.3390/pharmaceutics14091971 [ 87 ].…”