Acne is a common skin disease that arises from inflammation of the hair follicles and sebaceous glands. It is commonly found in areas with a high concentration of hair follicles and accumulated sebaceous glands, such as the face, neck, and upper torso. While it is most prevalent during adolescence, it can occur in other age groups as well. Some individuals may experience acne persistently into adulthood. The development of acne can be attributed to various factors, including increased sebum production, proliferation of the bacterium Propionibacterium acnes (P. acnes), inflammation of the skin, and thickening of keratin. Although acne is not a life-threatening condition, it can lead to the formation of persistent scars and non-healing dark spots [1]. Acne or acne scars can have an impact on emotions and mental well-being. Studies of the psychological effects of acne in individuals aged 15 and older have found that acne can lead to feelings of self-doubt, anxiety, social avoidance, and a reluctance to face others due to discomfort [2]. The treatment of acne requires time, and visible results may take some time to manifest.

Acne treatment is selected based on acne severity and lesion type and typically include topical, systemic, or combination therapies. For mild to moderate acne, first-line treatments include topical agents such as benzoyl peroxide (BPO), retinoids (e.g., adapalene, tretinoin), and topical antibiotics like clindamycin or erythromycin. Benzoyl peroxide acts as an oxidizing agent that reduces P. acnes load and resists bacterial resistance, while retinoids normalize follicular epithelial desquamation. Topical antibiotics are often used in combination with BPO to mitigate resistance development. In cases of moderate to severe acne, oral antibiotics (e.g., doxycycline, minocycline) are frequently employed due to their anti-inflammatory and bacteriostatic activity. Hormonal therapies (e.g., combined oral contraceptives, spironolactone) are used particularly in female patients, while isotretinoin remains the gold standard for recalcitrant nodulocystic acne, targeting all four pathogenic mechanisms. However, long-term use of antibiotics has been associated with increased resistance and systemic side effects [3]. Emerging strategies focus on natural compounds with antibacterial and anti-inflammatory properties, such as tea tree oil, green tea, aloe vera, neem, turmeric, rosemary, liquorice, eugenol, or mangosteen extract. Despite their promise, poor skin permeability and limited clinical translation remain challenges [4]. A study involving 13 types of herbal extracts for antibacterial activities against bacteria causing acne found that mangosteen extract contains important compounds such as mangostin and xanthone derivatives, which exhibit potent antibacterial effects. Mangosteen extract demonstrated the best inhibitory effects against P. acnes and Staphylococcus epidermidis, with the lowest minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values [5]. The antibacterial mechanism of α-mangostin was reported by disruption of cell membrane integrity and increasing cell membrane permeability [6].

Mangosteen (Garcinia mangostana Linn.) is a fruit commonly referred to as the “Queen of Fruits”. It is known for its deliciously sweet taste and is highly popular in the Asian region. In addition, mangosteen also possesses numerous medicinal properties. Research on extracts from mangosteen peel has identified active compounds belonging to the xanthone group, such as α-mangostin, β-mangostin, γ-mangostin, and gartanin. These compounds exhibit pharmacological properties that support various health benefits. High levels of xanthones in mangosteen have pharmacological effects, including promoting wound healing, inhibiting bacterial infections, combating inflammation caused by infections, and antioxidant properties [7,8]. There is scientific research on the application of α-mangostin extracts, known for their inhibitory effects on the growth of acne-causing bacteria, as an alternative in treating acne and in cosmetic formulations. However, there are challenges in developing formulations, such as low water solubility, which limits the penetration of the key therapeutic agent into the target cells in the deeper layers of the skin [9]. Therefore, developing formulations to enhance solubility can improve the delivery of α-mangostin from mangosteen peel extracts to the hair follicles and sebaceous glands, which are the primary targets for acne treatment.

Products design for topical use on the skin allow the active ingredients to permeate through the outermost layer of the skin (stratum corneum) and exert their biological effects in this layer or other layers of the skin, without being absorbed into the bloodstream. Medications can penetrate through the skin via various pathways, including direct cell penetration (transcellular), passage between cells (intercellular), and through skin appendages (appendageal route), utilizing one or a combination of these routes. Currently, there is ongoing development of drug delivery systems through the skin to enhance the targeted delivery of drugs or active substances to specific cells within the skin. These include delivering drugs to other target organs by allowing the drug to enter the bloodstream, using various techniques such as microneedle, electrical currents for molecular propulsion, chemical permeation enhancer, and particle systems such as liposomes, polymeric nanoparticles, [9].

Microneedles are a drug delivery system developed to enhance the capability of delivering drugs into the skin. The stratum corneum (SC) as an external layer of human skin is the principal barrier of substance permeation to enter the body. Microneedles are tiny needles at the micron level that can enhance drug delivery efficiency by piercing through the stratum corneum layer of the skin and creating small channels for drug delivery. Microneedles can be used to deliver small drug molecules, macromolecules, or nanoparticles, including substances with large molecular sizes that cannot pass through the stratum corneum via passive diffusion [10]. When comparing to conventional topical dosage form (creams, gels) or transdermal patches, which have been reported to deliver drugs at only 10–20 %, it is found that the use of microneedles is more effective than 2–5 times for delivering drugs into the stratum corneum layer [11]. Currently, microneedles can be classified into five types: solid microneedles, coated microneedles, dissolving microneedles, hollow microneedles, and hydrogel-forming microneedles. The dissolving microneedle (DMNs) is currently garnering increased interest in transdermal drug delivery. The inactive components of DMNs can be biocompatible and biodegradable polymers to ensure their safety for use. When the miniscule needles penetrate the skin, the polymer gradually dissolves and releases the drug from the needles. There are several advantages to this delivery technology, such as delivering the drug in a single step, and the ability to control the dissolution rate and drug release by adjusting the composition and content of the polymers [11,12]. Recent studies have demonstrated that DMNs are not only effective for transdermal delivery but also serve as promising platforms for localized drug release in wound environments, offering both antibacterial activity and tissue-regenerative capabilities [13,14]. Therefore, the development of transdermal drug delivery systems, such as DMNs, offers a promising platform to overcome the limitations of conventional topical treatments by enabling targeted, painless, and enhanced delivery of bioactive agents directly into the dermal layer, where acne pathology occurs.

Polymers used in the fabrication of DMNs serve as essential drug carriers to enhance the efficiency of drug delivery. Eudragit® RL was selected as a biocompatible and pharmaceutically accepted polymer, known for its permeability-controlling properties and ability to form stable films suitable for microneedle fabrication [15]. Hydroxypropyl methylcellulose (HPMC) is a biodegradable and biocompatible polymer that further supports the structural integrity and dissolution behavior of the microneedles [16]. In a previous study, utilizing Eudragit® RS100 or E100 polymers in combination with polyvinylpyrrolidone K-90 (PVP K-90) for microneedle fabrication, it was found that they could provide microneedles with suitable hardness. These microneedles demonstrated the ability to penetrate through the skin [17]. Additionally, there has been a study on utilizing HPMC polymer in conjunction with PVP for fabricating DMNs to enhance the efficiency of drug delivery. It was found that this combination of polymer type could successfully create microchannels with 100 % insertion on the skin surface, and the drug delivery was more effective compared to conventional topical formulations [18].

In recent years, DMNs have emerged as a versatile acne therapeutic technology due to their minimally invasive nature, effectiveness, and reduced side effects. DMNs facilitated targeted drug delivery to the deeper layers of the skin [19]. A recent study investigated azelaic acid-loaded dissolving microneedles (AZA-DMNs) as a self-administered, rapid-onset therapy for acne vulgaris. Unlike traditional solid microneedles, which carried risks such as needle breakage and required professional application, AZA-DMNs demonstrated excellent skin compatibility, notable antibacterial efficacy, and localized drug action with negligible systemic absorption. A randomized pilot study in adult acne patients revealed that AZA-DMN treatment resulted in a faster resolution of inflammation and significantly shortened the treatment cycle compared to commercial AZA creams. These findings supported the practicality, safety, and therapeutic advantages of dissolving microneedle platforms in acne management [20]. For natural compounds, researchers developed eugenol-loaded hyaluronic acid-based dissolving microneedles (E@P-EO-HA MNs), which combined photothermal therapy with transdermal drug delivery. These microneedles exhibited sufficient mechanical strength to penetrate the stratum corneum while providing sustained release of eugenol with both antibacterial and anti-inflammatory effects. Under near-infrared irradiation, the system effectively disrupted sebaceous glands and eradicated P. acnes, thereby promoting the repair of acne lesions. This dual-action approach exemplified the potential of multifunctional microneedle systems for targeted and synergistic acne therapy [21].

Recently, the development of mangosteen extract-loaded DMNs for acne treatment has been limited, with less study information available. Therefore, the objective of this study is to develop a formulation of mangosteen extract-loaded DMNs to enhance the delivery efficiency of mangosteen extract through the skin. In this study, mixed polymers from Eudragit® RL100 and HPMC 4000 were chosen to prepare the DMNs. The appropriate polymer mixing ratio was selected to fabricate DMNs with sufficient hardness and rapid dissolution. Physicochemical properties, loading efficiency, loading capacity, and skin permeation were investigated for the developed DMNs. The antibacterial efficacy of mangosteen extract-loaded DMNs was also evaluated.