The skin microbiome is a complex and dynamic ecology that resides in the skin, which is the largest organ of the human body. This varied group of microbes, which includes bacteria, fungi, and viruses, is essential to the homeostasis and health of the skin. A variety of skin diseases and disorders have been connected to disruptions of this critical microbial balance [1], such as psoriasis, vitiligo, and atopic dermatitis (AD) [2]. Promising new opportunities in the field of dermatology have recently arisen with the development of nanotechnology. Scientists and researchers have been investigating the development of innovative nanotechnology that provides efficacy in the restoration and control of the skin microbiome [3,4]. Nanoparticles can generally be utilized for delivering drugs in a way that improves their resistance to enzymatic degradation, targets specific locations, increases bioavailability, solubilizes them for intravascular transport, and maintains their effects [5]. These nanosystems or microbiome-targeted nanotherapeutics provide a novel approach that targets the related causes of skin disorders while reducing the adverse effects associated with traditional therapies.

The field of microbiome-targeted nanotherapeutics has been growing rapidly, and many nanosystems are being investigated for the regeneration and maintenance of the microbiota [6,7]. The nanostructures can be engineered to interact with the microbiome, either by modulating the microbial composition or delivering therapeutic agents that influence the microbiome, which affects the progression of certain skin conditions [8]. However, careful consideration of unexpected effects, biocompatibility, regulatory challenges, and long-term impacts is essential to ensuring the safety and efficacy of these innovative treatments [9]. Nanoparticles and nanoemulsions are the most popular nanosystems for targeting microbiomes because of their small size, modified properties, and efficient delivery capabilities. Their unique characteristics enable precise interactions with microbial communities and facilitate effective, customized interventions for improved dermatological treatments [3,10]. Nanoparticles typically range in size from 1 to 100 nanometers and are solid, colloidal particles. They can be made from a variety of materials, such as metals, polymers, and lipids. They include lipid nanoparticles (liposomes and solid lipid nanoparticles), polymeric micelles, metal nanoparticles, and polymeric nanoparticles (Figure 1). They are utilized in drug delivery since they may protect and deliver drugs to particular target locations within the body, enhancing medication effectiveness and minimizing adverse effects.

Furthermore, nanoparticles are employed to improve the performance of sunscreens, lotions, and other skincare products [11,12,13]. On the other hand, nanoemulsions are small oil droplets, typically ranging in size from 20 to 200 nanometers, distributed in an aqueous phase and frequently stabilized by surfactants in a process known as nanoemulsions formulations. They are either oil-in-water (O/W) or water-in-oil (W/O) nanoemulsions. The solubility and bioavailability of poorly water-soluble drugs can be enhanced by using nanoemulsions. In addition, they are used to improve the stability of some products as well as to encapsulate flavors, vitamins, and other bioactive components. In cosmetics, nanoemulsions are utilized in order to enhance the texture and stability of lotions and skincare items [14,15]. When creating medications in nanoform to increase absorption and effectiveness, three main variables need to be considered. These include FDA quality-related standards, drug transport, degradation mechanisms, and the stability of the manufactured drug. The pharmaceutical industry has limitations while utilizing nanoformulations because of this. The primary cause of the low therapeutic efficacy of nano-formulations is their propensity to self-aggregate at low drug concentrations, which compromises the formulation’s stability and increases the variability of drug entrapment because of polydispersity. Unformulated liposomes are more stable, but when a medicine is built into them, the stability decreases as the ionic strength grows. Starting with smaller nanoparticles (<20 nm) for the formulation could solve this issue such that even after loading the drug, it remains below 100 nm [16,17]. Although around 100 nm-sized nanoparticles have increased surface reactivity, they can have adverse biological effects like protein unfolding, membrane impairment, DNA damage, and inflammatory reactions. Additionally, several size-dependent processes, such as clathrin-mediated entry and caveolae-mediated pathways, allow particles in the 10–500 nm range, including those about 100 nm, to be absorbed into cells. Particle size preferences vary throughout cells; endothelial cells prefer particles that are around 100 nm in size, while professional phagocytes prefer larger particles [18,19].

Oxidative stress affects mitochondrial function and promotes the production of reactive oxygen species (ROS) and pro-inflammatory cytokines [20]. Increased ROS in the skin destroys melanocytes by damaging their DNA and associated cellular structures [21]. In addition, ROS causes a variety of oxidation products, including oxidized protein products and glycation products, that alter the structure of melanocytes [22]. It has been suggested that the main cause of melanocyte loss is mitochondrial malfunction driven by oxidative stress. Increased carbonylation in vitiligo melanocytes causes mitochondrial dysregulation, which could lead to severe mitochondrial dysfunction and melanocyte apoptosis [23]. The microbiome may influence the skin’s general durability and response to oxidative stress or contribute to the modulation of oxidative stress and inflammation [24].

In the exploration of skin health, emerging research underscores the role of the skin microbiome in various dermatological conditions. Among these conditions, vitiligo is an autoimmune condition characterized by depigmented macules and patches of various forms, which is caused by the death of melanocytes or the loss of their activity to produce natural skin pigments [25]. Consequently, discolored white spots appear on the skin, hair, and mucous membranes in various parts of the body. The prevalence of vitiligo in the general population of the world ranges from 0.06% to 2.28% [26]. Vitiligo can be classified into different types based on the characteristics of the lesions. Acrofacial vitiligo is characterized by lesions occasionally appearing on the extremities and face. Mixed vitiligo involves a combination of non-segmental and segmental patterns. Focal vitiligo is distinguished by small and isolated lesions. Mucosal vitiligo occurs in or around mucosal membranes. Universal vitiligo is a type where lesions develop and spread over the entire body [27,28]. Numerous mechanisms have been connected to the degeneration of melanocytes and the emergence of white patches in vitiligo. These mechanisms include neuronal, genetic, autoimmune, oxidative stress, environmental triggers, and the creation of inflammatory mediators [29]. The most prevalent and well-established explanation proposes that a defect in the immune response results in the destruction of melanocytes by autoimmune effector mechanisms, either memory cytotoxic T cells or autoantibodies directed against melanocyte surface antigens. Numerous studies have demonstrated a link between vitiligo and other autoimmune diseases such as Addison’s disease, pernicious anemia, diabetes, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and alopecia areata [30,31]. Topical corticosteroids (TCSs) and Topical calcineurin inhibitors (TCIs) are often used and recognized as a common treatment for many types of vitiligo [32]. When concerns regarding the reported adverse effects of prolonged usage of potent TCSs and TCIs arise, both have demonstrated a high degree of repigmentation but are not safe treatment options. TCIs often result in erythema, pruritus, and burning sensations as side effects, while TCSs increase the possibility of skin atrophy, striae, and telangiectasia [33,34]. Alternative treatments and outcomes have improved as a result of the introduction of numerous therapeutic approaches, such as phototherapy, excimer laser, vitamin D, and epidermal grafts [35,36]. However, there is occasionally hesitancy to suggest treatment because, historically, vitiligo was thought to respond to treatment quite poorly and infrequently [37]. Another common pathogenic trigger for melanocyte destruction in vitiligo patients is oxidative stress, which is also a key element in the onset and progression of the disease [38].

Psoriasis is a chronic inflammatory skin disease developed by the influence of a genetic predisposition and external variables. It has several different kinds; however, they are all identified by erythematous plaques that are frequently itchy [39]. The cutaneous immune system’s improper activation against a presumed infection is the main theory regarding the development of psoriasis. The innate and adaptive immune systems are both implicated in the pathogenesis of the disease, which also involves abnormal keratinocyte development and immune cell infiltration in the dermis and epidermis, with dendritic cells and T cells performing significant roles [40].

AD is the most prevalent inflammatory skin disorder worldwide. It affects a substantial portion of the global population, impacting around 15% to 20% of children and 1% to 3% of adults [41]. This chronic inflammatory skin condition is characterized by itchy and dry inflamed lesions. It stems from a range of hereditary mutations in skin barrier proteins and immunological defects specific to allergens. Individuals with AD often exhibit symptoms such as skin dryness, redness, and the development of erythematous lesions. Moreover, AD frequently presents with related issues like eczema, skin scaling, and persistent itching. Additionally, it can be associated with comorbidities such as allergic rhinoconjunctivitis and asthma [42].

Recently, evidence showed that altered skin microbiomes (dysbiosis) contribute to the pathogenesis of vitiligo by influencing immunological homeostasis, oxidative stress, and skin barrier [43,44]. Further, research on the skin lesions of psoriasis patients has revealed an imbalance in the skin microbiome. The authors report that inflammation results from a dysbiosis disruption of the skin’s immunological responses. Streptococcus bacteria are frequently overabundant, while Cutibacterium is less present in these lesions [39]. Studies are increasingly focusing on combining probiotics and nanotechnology to treat skin infections. Improved drug delivery, moisture retention, controlling the release of active compounds, and anti-infective properties have been demonstrated by nanotechnology, especially nanoparticle-based methods [45]. Some research suggests that topical probiotics emollient and bacteria-derived formulations may be an effective alternative for the treatment of AD [46]. Due to their capacity to have a favorable effect on the skin microbiome, these formulations can decrease inflammation and enhance the general health of the skin barrier by creating a balance in the microbial communities on the skin. [47]. Additionally, the controlled probiotic release offered by nanoparticles and nanotechnology delivers enormous potential for treating human infections. Although beneficial results have been observed, further human research is required to investigate their effectiveness in dermatological applications and to address the problem of bacterial resistance [48,49].

2. Prebiotics, Probiotics and Postbiotics

3. Skin Microbiome

4. Mechanisms of Action for Topical Prebiotics, Postbiotics and Probiotics

5. Clinical Verification and Effectiveness