Novel Formulation of Fusidic Acid Incorporated into a Myrrh-Oil-Based Nanoemulgel for the Enhancement of Skin Bacterial Infection Treatment

Abstract

Fusidic acid (FA) is renowned as an effective bacteriostatic agent obtained from the fungus Fusidium coccineum, used for treating various eye and skin disorders. The objective of the present study was to develop, characterize, and evaluate the antibacterial activity of a novel FA nanoemulgel for topical skin application. Primarily, various fusidic acid nanoemulsion formulations were fabricated using different concentrations of myrrh essential oil, Tween 80 as a surfactant, and Transcutol® P as a co-surfactant. A Box−Behnken design was employed to select the optimized FA nanoemulsion formulation, based on the evaluated particle size and % of in vitro release as dependent variables. The optimized formula was incorporated within a hydrogel to obtain an FA nanoemulgel (FA-NEG) preparation. The formulated FA-NEG was evaluated for its visual appearance, pH, viscosity, and spreadability, compared to its corresponding prepared fusidic acid gel. In vitro release, kinetic study, and ex vivo drug permeation were implemented, followed by formulation stability testing. The FA-NEG exhibited a smooth and homogeneous appearance, pH value (6.61), viscosity (25,265 cP), and spreadability (33.6 mm), which were all good characteristics for appropriate topical application. A total of 59.3% of FA was released from the FA-NEG after 3 h. The ex vivo skin permeability of the FA-NEG was significantly enhanced by 3.10 ± 0.13-fold, showing SSTF of 111.2 ± 4.5 µg/cm2·h when compared to other formulations under investigation (p < 0.05). No irritation was observed upon applying the FA-NEG to animal skin. Eventually, it was revealed that the FA-NEG displayed improved antibacterial activity against a wide variety of bacteria when compared to its corresponding FA gel and marketed cream, indicating the prospective antibacterial effect of myrrh essential oil. In conclusion, the recommended formulation offers a promising antibacterial approach for skin infections.

Keywords: antibacterial; fusidic acid; myrrh essential oil; nanoemulgel; optimization.

Figure 1

2D contour graphs demonstrating the influence of the independent factors (A) X₁ and X₂, (B) X₁ and X₃, and (C) X₂ and X₃ on particle size responses (R₁).

Figure 2

3D response surface plots demonstrating the influence of the independent factors (A) X₁ and X₂, (B) X₁ and X₃, and (C) X₂ and X₃ on particle size responses (R₁).

Figure 3

Predicted versus actual plot representing the linear correlation between values for particle size response (R₁).

Figure 4

In vitro release of FA from various NE formulations kept at 32 °C using pH 5.5 phosphate buffer for 6 h. Results are presented as the mean values of three determinations ± SD.

Figure 5

2D contour graphs signifying the influence of the independent factors (A) X₁ and X₂, (B) X₁ and X₃, and (C) X₂ and X₃ on in vitro release response (R₂).

Figure 6

3D response surface plots signifying the influence of the independent factors (A) X₁ and X₂, (B) X₁ and X₃, and (C) X₂ and X₃ on in vitro release response (R₂).

Figure 7

Predicted versus actual plot representing the linear correlation between values for in vitro release response (R₂).

Figure 8

Optimization figures screening the influence of (A) X₁ and X₂, (B) X₁ and X₃, and (C) X₃ and X₂ on overall desirability.

Figure 9

Outline of in vitro release of FA from FA-G and FA-NEG compared to FA as a free drug, using pH 5.5 phosphate buffer at 32 ± 0.5 °C. Results are expressed as the mean ± SD of three trials; * p < 0.05 compared to free FA; @ p < 0.05 compared to the FA-G formulation.

Figure 10

Percentage of drug released from developed FA formulations against free FA, and their kinetic analysis, according to (A) zero-order (B) first-order, (C) Higuchi, and (D) Korsmeyer–Peppas models.

Figure 11

Outline of stability studies for (A) FA-G and (B) FA-NEG formulations for 1 and 3 months at 4 °C and 25 °C in terms of in vitro drug release, compared to their corresponding freshly prepared formulations. Data are expressed as means ± SD for three experiments.

Figure 12

Ex vivo permeation study profile of FA from diverse preparations (free FA, FA-G, and FA-NEG) across a rat skin membrane. Results are expressed as means ± SD (n = 3); * p < 0.05 compared to free FA; # p < 0.05 compared to the FA-G formulation.

Figure 13

Inhibition zone diameters caused by various formulations—(A) FA-NEG, (B) placebo NEG, and (C) marketed FA—on different organisms: (1) Bacillus subtilis, (2) Staphylococcus aureus, (3) Enterococcus faecalis, (4) Candida albicans, (5) Shigella, and (6) Escherichia coli.