Antibiotic resistance represents a major global healthcare challenge [1]. Resistance has affected almost all clinically used antibiotics, largely due to antibiotic overuse and misuse, as well as various social, economic and environmental factors [2]. Other factors like climate, health care quality, and migration were also reported to contribute to the problem [3,4]. Overuse of antibiotics has also contributed to the development of bacterial strains that are resistant to most known treatment regimens, leading to failure of drug therapies [5]. In 2019 there were approximately 1.27 million deaths attributed to bacterial antimicrobial resistance [6]. One of the important approaches to overcome this problem is exploring alternative remedies such as those based on natural products. Thus, essential oils derived from natural sources showed significant promise as potential antibacterial agents with lower risk of bacterial resistance, offering substitutes to conventional antibacterial agents [7,8].

Fusidic acid (FA) is an antibacterial drug obtained naturally from the fungus Fusidium coccineum with a tetracyclic triterpenoid structure [9,10]. It exhibits effectiveness against Gram-positive bacteria, mostly Staphylococcus aureus and Staphylococcus epidermidis [11]. It can inhibit growth of bacteria by attaching with bacterial ribosomes and preventing translocation of the peptide leading to prevention of protein synthesis. At low concentrations, it acts as a bacteriostatic agent whereas at higher ones it becomes potentially bactericidal [12]. FA is available in the market in several dosage forms for intravenous, oral and topical use [13]. However, topical application is preferred for the treatment of skin infections due to increased drug concentration at the disease site [14]. FA is classified as a Biopharmaceutics Classification System class II drug based on its high permeability and low solubility [15]. The hydrophobic nature of FA presents a great obstacle to its incorporation into pharmaceutical dosage forms, leading to limited therapeutic efficacy. Moreover, the natural resistance of Gram-negative bacteria significantly limits its clinical effectiveness in the treatment of infections caused by these pathogens [16]. Consequently, innovative drug delivery approaches are essential to address these challenges and overcome the bacterial resistance.

Myrrh is a yellow color oleo-gum resin obtained from plants stem of the genus Commiphora, particularly Commiphora molmol and Commiphora myrrha (Burseraceae family) [17]. Myrrh consists of essential oils, water-soluble gum (30–60 %), ether-soluble myrrhol (3–8 %), and an alcohol soluble resin, myrrhine (25–40 %) [17]. Myrrh also contains cuminic aldehyde, terpenes, eugenol, and sesquiterpenes [18]. Myrrh oil, the essential oil derived from the resin of the Commiphora myrrha tree was found to possess broad-spectrum therapeutic activities including antibacterial, anticancer, antinociceptive, anti-inflammatory, antioxidant and anti-ulcer [19]. Additionally, it was found that Commiphora molmol has a potent cytotoxic activity against Ehrlich ascites carcinoma with an activity similar to that of cyclophosphamide [20]. It also protects against oxidative stress due to its free radical scavenging properties, which provides protection against the lipid peroxidation effect caused by some lipophilic pharmaceuticals and different cosmetic preparations [21]. Myrrh oil exhibited moderate activity against E. coli and Salmonella species but no activity against Pseudomonas species using the inhibition zone method [22]. Its minimal bactericidal concentration against Gram-positive bacteria was ≤0.2 % (v/v) while against Gram-negative bacteria it was 0.8 % for Pseudomonas species [22]. It is therefore hypothesized that combining myrrh oil and FA in an appropriate delivery system could enhance the antibacterial efficacy of FA and broaden its spectrum through synergistic or additive effects. This is particularly important given the Gram-negative bacterial resistance to FA.

Organogels are semisolid dosage forms containing a gelator and a non-polar solvent (an organic solvent or an oil) immobilized within a three-dimensional network structure [23,24]. Gelators frequently used for organogel preparation are lecithin, sterols, and fatty acid esters, such as sorbitan esters [25]. Organogels have distinct advantages such as ease of preparation and long-term stability, leading to increased interest in their use for drug delivery [26,27]. The incorporation of an organogelator transforms liquid oil into a cohesive, gel-like structure, which enables the direct conversion of oils into gels without the need for water or polymers, unlike conventional hydrogels [28]. Organogels offer distinct advantages when using pharmacologically active oils, such as myrrh oil, as they preserve the oil therapeutic properties and allow the incorporation of a significantly higher oil content of up to approximately 70 % [25]. In contrast, emulsions and creams generally have limited oil content due to stability issues. This high oil-loading capacity is especially valuable when the oil itself has pharmacological properties, such as essential oils, where maximizing oil concentration is beneficial therapeutically. Additionally, organogels offer improved formulation stability due to the absence of water, which reduces the risk of microbial contamination and enhances the solubility and loading of lipophilic drugs [29,30]. These distinct advantages highlight the rationale for selecting organogel in this study as a delivery system to fully exploit the pharmacological potential of myrrh oil and FA. To date, the literature shows a very limited number of studies investigating the combination of FA and myrrh oil in any pharmaceutical dosage form. While both agents have been individually tested for their antimicrobial and wound-healing properties, their combination remains a new area of research, highlighting the novelty and potential impact of this study. Thus, Almostafa et al. prepared a myrrh oil-based nanoemulgel for topical FA delivery [31]. They showed that the nanoemulgel exhibited improved FA skin permeation and antibacterial efficacy compared with FA commercial cream and control FA gel.

The current study is an attempt to enhance FA wound-healing properties and antibacterial activity against Gram-positive bacteria and reverse the resistance of Gram-negative bacteria through loading into a myrrh oil-based organogel. This approach, which uses a biologically active excipient, capitalizes on the natural antibacterial, anti-inflammatory and antioxidant properties of myrrh oil, ultimately leading to improved wound-healing efficacy of the FA organogel. The organogels were prepared using different gelators and characterized using various techniques. In vitro antibacterial activity was tested against several Gram-positive and Gram-negative bacterial strains. Additionally, the wound-healing efficacy was evaluated in a rat wound model.