Acne vulgaris, commonly referred to as acne, is a chronic inflammatory skin condition that mainly affects adolescents, with the highest prevalence between 12 and 18 years of age, although it may persist or newly develop in adults, particularly those aged 20–40 years [1]. Acne can be attributed to various factors, including hormonal, dietary, genetic, immunological and environmental [2]. This is translated in the body as excessive secretion of sebum and ductal hypercornification, resulting from the abnormal buildup of keratinocytes, which leads to clogged pores that form blackheads and whiteheads. It also appears as microbial flora changes, mainly related to the colonisation of bacteria, which leads to the formation of inflammatory byproducts that, along with the body's immune response, trigger inflammation [3], [4], [5].

The origin of acne development can be attributed to a disturbance in the skin microbiome, resulting in the alteration of the proportions of certain bacterial species, such as Cutibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis [6]. This condition is known as skin dysbiosis and may also contribute to the development of other skin diseases, including atopic dermatitis, psoriasis, dandruff, or even skin cancer [7]. Although Cutibacterium acnes is widely regarded as a central factor in acne pathophysiology, current evidence indicates that disease severity depends not only on bacterial load but also on strain-specific characteristics and shifts in the overall microbial balance. Moreover, other members of the skin microbiota, such as Staphylococcus epidermidis and Staphylococcus aureus, can contribute to inflammatory responses and secondary infections, particularly when the skin barrier is impaired [8], [9], [10]. Staphylococci produce several virulence factors, such as toxins and enzymes, that facilitate colonisation and invasion of the human organism [11]. These bacteria play a pathogenic role in the development of atopic dermatitis, psoriasis, and acne vulgaris [12], [13]. Recent studies indicate an increased contribution of S. aureus and S. epidermidis to the pathogenesis of acne. A 2024 cohort study involving 36 healthy volunteers aged 22–39 years demonstrated that C. acnes is present on both healthy and acne-affected skin; however, its abundance was more than twice as low on acne-affected skin. In contrast, a significant increase in the abundance of staphylococci was observed in acne lesions. Notably, the study found that for every single.

C. acnes cell on acneic skin, there were approximately eleven S. aureus cells. These findings indicate a significant shift in the balance of the acne skin microbiome, showing the critical role of staphylococcal species in the pathogenesis of acne [14]. The authors explain that the changes in the microbiome are associated with antibiotic therapy. Isotretinoin is recognised as one of the most effective acne treatments. It reduces sebum production, which significantly influences the composition of the skin microbiota [14], [15]. Alterations in the skin microbiome, characterised by increased alpha diversity, cause an increase in abundance of bacteria from other genera, predominantly Staphylococci [15]. Thus, in the context of studying skin infections, it is reasonable to consider extending the investigation to include biological models beyond C. acnes, such as Staphylococci strains.

The present study examines Staphylococcus species as opportunistic pathogens that can aggravate inflammatory skin conditions and contribute to complications in acne lesions, particularly when the skin barrier is compromised. This model enables assessment of the antibacterial activity of the developed formulation against clinically relevant Gram-positive bacteria.

Various therapies have been used to treat acne vulgaris. Topical treatments like benzoyl peroxide (BPO), retinoids, and antibiotics have been used to treat acne vulgaris for several decades [16]. However, the increase in antimicrobial resistance presents a challenge in reaching an effective treatment [17]. Antimicrobial resistance has become an increasingly important issue in the treatment of acne vulgaris and other dermatological conditions in which antibiotics are commonly prescribed. Long-term and repeated use of topical agents such as clindamycin and erythromycin, as well as systemic tetracyclines, has contributed to the emergence of resistant strains of C. acnes [18], [19]. The clinical effectiveness of these therapies declines, leading to reduced treatment response and, in some cases, persistent or recurrent inflammation.

In addition, antibiotic abuse in acne may promote resistance in other members of the skin microbiota, including S.aureus, which has broader implications beyond acne management [20]. Similar patterns are observed in diseases such as rosacea, impetigo, and atopic dermatitis, where antibiotic exposure can select for resistant organisms [21], [22]. These challenges underscore the importance of more judicious antibiotic use in dermatology, including limiting treatment duration, avoiding monotherapy, and prioritising non-antibiotic alternatives or combination regimens that help reduce the risk of resistance development [23], [24].

Additionally, the combination of retinoid formulations and BPO leads to several problems, such as reduced effectiveness due to their mutual reactivity and low tolerability [25]. That is why new alternative therapies are needed in this sector.

It is important to recognise that modern therapeutic approaches using natural products need to consider the changes in the skin microbiome caused by commonly used antibiotic treatments. In this context, several naturally derived compounds have been investigated as potential alternatives to antibiotic therapy in acne vulgaris due to their antimicrobial and anti-inflammatory activity [26], [27]. For instance, tea tree oil (Melaleuca alternifolia) exhibits activity against C.acnes and has demonstrated clinical efficacy in reducing inflammatory lesions in patients with mild to moderate acne [28]. Green tea extracts, particularly those rich in epigallocatechin-3-gallate (EGCG), have also shown promising results. Beyond their antioxidant properties, these compounds may reduce sebum production and downregulate inflammatory mediators involved in acne pathogenesis [29]. Propolis represents another natural substance of interest, with documented antibacterial and anti-inflammatory effects [30]. Aloe vera, although not primarily antimicrobial, may support barrier repair and reduce irritation when used alongside active treatments [31]. While these agents are not direct substitutes for systemic therapy in severe cases, they may serve as adjuncts or alternatives in mild to moderate acne, particularly where reduction of antibiotic exposure is desirable [32], [33]. Their incorporation into treatment strategies may help limit selective pressure for resistant strains while addressing multiple pathogenic mechanisms involved in acne vulgaris [34].

In this study, the antibacterial activity was assessed on bacteria from the Staphylococcus genus. Our intention was not to diminish the role of C. acnes, but to evaluate the antibacterial activity of the developed formulation against selected Gram-positive skin-associated bacteria that may contribute to inflammation and secondary infection.

The natural compounds isolated from plants, especially essential oils, exhibit the potential to inhibit and treat infections caused by different bacterial and fungal species. Essential oils were shown to have some interesting properties like antioxidant, anti-inflammatory, and antibacterial effects, specifically against strains causing acne [35], [36]. Specifically, lavender oil (LO), extracted from the flowers of Lavandula angustifolia, stood out as a potential candidate in dermatological applications due to its various properties. For example, Rai et al. proved that linalool (20–45%) and linalyl acetate (25–46%), the two major components of the LO, are effective in the treatment of psoriasis-like skin inflammation [37], [38]. It was also shown to have potential in wound healing applications [39]. Other studies also showed the effectiveness of LO against acne bacterial strains. For instance, Liu et al. showed that linalool had an inhibitory and bactericidal effect on S. aureus microbial strains [40]. Moreover, Soković et al. also proved that the LO had antibacterial activity against S. epidermidis and S. aureus strains [41]. On the other hand, it has been reported that when LO is exposed to air, it is readily oxidised and can form strong allergens leading to dermatitis. Hence, encapsulation would be the best way to deliver LO for acne applications since in this way it can be protected: thus, its volatility and oxidation decrease while it keeps its antibacterial properties. Prior studies have demonstrated the effectiveness of LO encapsulation; nevertheless, some suffered from low encapsulation efficiency [42], while others required the preparation of more complex structures, such as the double-layered microcapsules prepared by Zhang et al. or the liposomes encapsulated in chitosan beads reported by Liu et al [43], [44].

The use of biopolymers as encapsulation materials has attracted growing interest owing to their diverse physicochemical and functional properties [45]. Alginate is a natural, non-toxic anionic polysaccharide that can crosslink to form a gel in the presence of polyvalent cations [46]. Through the egg-box model, the carboxylic groups of the alginate chains interact with the polyvalent cations to form a crosslinked complex [47]. This gives the resulting hydrogel distinctive properties, enabling it to encapsulate a wide range of compounds by entrapping them within its network, protecting them from degradation, and allowing their controlled release over time [45], [48]. Several divalent cations have been used to crosslink the alginate, most importantly calcium [49]. Calcium alginate is widely used in dermatological applications. Compared to other divalent ions, calcium ions enable the formation of a stable alginate matrix that effectively protects the wound surface. In addition, calcium plays an important role in the coagulation cascade, which supports the haemostatic properties and clinical safety of calcium alginate materials [50]. Various studies have reported that calcium signalling can influence the production of pro-inflammatory cytokines implicated in acne pathogenesis. [51], [52]. However, this effect depends mainly on the concentration and the specific biological setting. Physiological levels of Ca2+ are required for proper epidermal differentiation and maintenance of the skin barrier, whereas excessive or uncontrolled calcium influx may promote inflammatory responses [53]. Therefore, the potential pro-inflammatory effect of calcium release from the capsules should be interpreted cautiously and in relation to the local concentration and biological model used.

Although alginate-based systems and essential oil-loaded formulations have been widely investigated, direct comparison of divalent crosslinking ions within the same microcapsule platform remains limited. In particular, the influence of Ca2+ versus Zn2+ crosslinking on matrix structure, release behaviour, antibacterial activity, and biological response has not been systematically evaluated. The present study addresses this gap by comparing calcium- and zinc-crosslinked alginate microcapsules loaded with lavender essential oil under identical formulation conditions. Additionally, to the best of our knowledge, this is the first report describing this system as a potential treatment for acne targeting selected Gram-positive bacteria associated with the skin.

We propose the use of zinc as a crosslinker due to its known antibacterial effect and its activity against acne [54], [55]. Actually, people with acne usually exhibit lower zinc levels, and it was shown that oral and topical supplementation with zinc decreased the number of inflammatory papules, ensuring its role in acne therapy [56]. On the other hand, zinc oral supplementation presents adverse effects like nausea, vomiting and stomach cramps, while topical use should be accompanied by hydrating bases since it can provoke irritation and erythema [55].

To address the previously reported challenges, we aimed to encapsulate LO using a simple, scalable, and cost-effective procedure while achieving a high encapsulation efficiency. In a previous paper [57], we prepared alginate capsules crosslinked by zinc ions and encapsulating LO, based on nanoemulsion and ionic gelation (Fig. 1). These capsules were compared to reference capsules crosslinked by calcium. The capsules were characterised thermogravimetrically, morphologically, and mechanically.

Considering the antibiotic resistance in microorganisms causing acne and the diversity of the microorganism species involved in skin infections, this study aims to investigate the susceptibility of S. aureus and S. epidermidis strains to the encapsulated LO and the possible improved effect resulting from LO and the cation. From a biopharmaceutics perspective, topical delivery systems must balance drug stability, release kinetics, biological activity, and cellular tolerance [58].