Acne vulgaris is one of the most prevalent skin disorders worldwide and the most common skin condition associated with inflammation of the pilosebaceous unit; it affects all ethnic and age groups, independent of sex, nationality, or socioeconomic status [1] [2] [3] [4]. The incidence in adult women is around 12% and among adolescents of 12 - 18 years old, more than 85% [5] [6].

The presence of acne lesions can usually affect self-confidence, anxiety, and community avoidance [7]. Additionally, it can also affect the sexual quality of life of adult patients [8].

In addition, relapses are frequent (44%; 39.9% of ≤20-year-old vs. 53.3% of >20-year-old) and often associated with impaired quality of life and decrease in productivity or even absenteeism [9]. There is also evidence that acne vulgaris can impact the difficulties in emotion regulation (DER), notably anxiety and depression [10] [11].

This occurs because acne lesions can become scarring, which can aggravate both the physical aspect of the patient as well as the impact on the psychological factors.

The current body of possible treatments includes oral, physical, and topical strategies. Oral treatments include antibiotics, hormonal agents, or isotretinoin, while physical interventions can be peelings and laser therapy. In addition, topical treatment may include antibiotics, benzoyl peroxide, dapsone, retinoids, or azelaic acid [12]. A recent systematic review and network meta-analysis showed that topical benzoyl peroxide was effective for improving self-reported acne, as well as its combination with adapalene or with clindamycin [13].

Those topical treatments can be obtained through commercial preparations in fixed doses or as compounded creams/gels, with personalized qualitative and quantitative composition, to be unique to each patient. Compounded treatments are an important resource for patient care [14]. However, developing semisolid dosage forms with proven stability, compatibility with a broad range of active pharmaceutical ingredients (APIs), and sensory and functional characteristics adequate to the patients, can be challenging to the compounding pharmacies worldwide. In this sense, ready-to-use vehicles play an important role as a timesaving strategy and to ensure maximum results from the treatment. In this paper, we present Cleoderm^TM Clarifying Cream, a ready-to-use, functional semisolid vehicle for acne treatments and topical products for oily skin, to be used by compounding pharmacies. We discuss the rationale behind its composition and its benefits for acneic skin.

To understand the functional aspects of the ready-to-use vehicle Cleoderm^TM Clarifying Cream, it is important to understand the multifactorial etiology of acne—although such mechanisms are not yet fully elucidated.

Acne can be understood as an inflammatory disease that affects the pilosebaceous follicle [15]. The common skin manifestations are comedones, papules, pustules, cysts, nodules, and scars [16]. Acne scars can be divided into three main groups: icepick scars, rolling scars, and boxcar scars (Figure 1), as well as some less common lesions such as sinus tracts, hypertrophic scars, and keloidal scars.

The main etiological accepted mechanism involves changes in the pilosebaceous unit through the hyperkeratinization of the pore, overproduction of sebum, and excessive proliferation of Cutibacterium acnes (formerly known as Propionibacterium acnes, an anaerobic lipophilic bacteria)—this would lead to the inflammatory processes due to the blocking of the hair follicle [17] [18].

It seems that the initial process is the formation of micro comedones, which evolves to macro (visible to the naked eye) comedones (blackheads or whiteheads) and can develop into inflammatory red papules or pustules—usually on the face, neck, chest, and upper back, where the number of sebaceous follicles is higher (Figure 2). These lesions can then be resolved or develop complications, leading to the emergence of scars, both atrophic or hypertrophic [20].

The microbiome balance is important because the skin is also colonized by other microorganisms, such as Staphylococcus epidermidis and Streptococcus pyogenes. While S. epidermitis limits the number of C. acnes in the skin (by the release of succinic acid and suppression of IL-6 and TNF-α production), C. acnes also limits S. aureus and S. pyogenes (by the maintenance of acidic pH of the pilosebaceous follicle, through the propionic acid secretion). Thus. dysbiosis can affect the skin barrier and cause inflammation [15] [23].

The fungus Malassezia furfur is also involved in the process, as it can decompose fatty acids and release irritant chemicals to the skin, in addition to the secretion of allergenic proteins and peptides [24]. However, both organisms exist in a commensal relationship in healthy skin, and then the intricated microbiome-microbiome and microbiome-host interactions are more prone to be a causal factor than the simple colonization by one of these organisms [23].

Sebum production is highly implicated in acne pathophysiology, and to date, it is known that it can be induced by six receptors expressed in the sebaceous gland (Figure 3):

· Histamine receptor—activated by histamines [25];

· Hormonal DHT receptor—activated by androgens [26];

· Neuromodulator receptor (substance P and corticotrophin-releasing hormone (CRH) receptor)—activated by stress [27];

· Peroxisome proliferator-activated receptors (PPARα, β, and γ)—activated by free fatty acids and cholesterol [28];

· Insulin-like growth factor (IGF)-1 receptor—activated by sugar [29];

· Leptin receptor—activated by fat [30];

The last three are therefore correlated to the diet of the patient. Situations such as peripheral hyperandrogenemia (particularly in women) can abnormally activate the androgens receptors [15].

Another possible player in acne vulgaris development is the endocannabinoid system in the skin, which can be involved in different processes, such as the differentiation of cells of appendages such as the sebaceous gland. Additionally, it also appears to be involved in sebum secretion control [31].

The immune system can also play a role in acne emergence (Figure 4). C. acnes can promote the release of Th17/Th1-related cytokines, specially IFN-γ and IL-17A. [32] The activation of the innate immunity (via the production of IFN-γ, IL-8, IL-12, TNF, IL-1, and MMPs) can result in the hyperkeratinization of the pilosebaceous unit [15].

AP: activator protein, FFA: free fatty acid, IL: interleukin, MMP: matrix metalloproteinases, NF: nuclear factor, PMNs: polymorphonuclear leukocytes, TLR: toll-like receptor, TNF: tumor necrosis factor.

Finally, the concept of exposome is also being introduced to acne research. Exposome can be understood as the sum of internal and external exposures that the person is exposed from conception until death [34]. In this context, researchers have demonstrated that the main internal factors related to acne are:

· C. acnes abnormal proliferation in the skin, due to dysbiosis;

· Elevated sebum production;

· Alteration of follicular epithelium (hyperkeratinization, due to hyper seborrhea);

· Inflammatory processes, both in innate and acquired immunities [35] [36].

In addition, the external factors that can play a role in both the severity and treatment efficacy of the disease are [37] [38]:

· Nutrition (diet);

· Medication;

· Stress;

· Occupational factors;

· Pollutants;

· Sun exposure;

· Weather factors (such as temperature and humidity);

· Psychosocial and lifestyle parameters.

Cleoderm^TM Clarifying Cream is a functional vehicle with selected ingredients that makes it the ideal choice for compounding acne topical treatments. Its main constituents are Cleome gynandra L. leaf extract, Palmitoyl Tripeptide-8, Bisabolol, Hyaluronic acid, and a blend of 8 functional oils (Perseagratissima, Simmondsiachinensis, Rosa canina, Cocosnucifera, Lavandulaangustifolia, Melaleucaalternifolia, Rosmarinusofficinalis, Vitellariaparadoxa, and Tocopherylacetate).

In addition, it is free from dyes, parabens, mineral oil, sodium lauryl sulfate, propylene glycol, and petrolatum.

The current body of evidence shows that Cleoderm^TM Clarifying Cream is an important solution for the production of treatments for acneic and oily skin in the context of personalized medicine. Its compatibility with a broad range of active ingredients, together with its functional ingredients, makes it a prominent vehicle for compounding pharmacies.

The authors declare no conflicts of interest regarding the publication of this paper.

Polonini, H., Zander, C. and Radke, J. (2021) Cleoderm^TM Clarifying Cream: A Novel, Topical Vehicle Using Plant-Based Excipients and Actives Targeting Acne and Oily Skin. Journal of Cosmetics, Dermatological Sciences and Applications, 11, 381-399. https://doi.org/10.4236/jcdsa.2021.114031