Transcutaneous penetration of a single-chain variable fragment (scFv) compared to a full-size antibody: potential tool for atopic dermatitis (AD) treatment.

Currently, several biologics are used for the treatment of cutaneous pathologies such as atopic dermatitis (AD), psoriasis or skin cancers. The main administration routes are subcutaneous and intravenous injections. However, little is known about antibody penetration through the skin. The aim was to study the transcutaneous penetration of a reduced-size antibody as a single-chain variable fragment (scFv) compared to a whole antibody (Ab) and to determine its capacity to neutralize an inflammatory cytokine involved in AD such as human interleukin-4 (hIL-4). Transcutaneous penetration was evaluated by ex vivo studies on tape-stripped pig ear skin. ScFv and Ab visualization through the skin was measured by Raman microspectroscopy. In addition, hIL-4 neutralization was studied in vitro using HEK-Blue™ IL-4/IL-13 cells and normal human keratinocytes (NHKs). After 24 h of application, analysis by Raman microspectroscopy showed that scFv penetrated into the upper dermis while Ab remained on the stratum corneum. In addition, the anti-hIL4 scFv showed very efficient and dose-dependent hIL-4 neutralization. Thus, scFv penetrates through to the upper papillary dermis while Ab mostly remains on the surface, the anti-hIL4 scFv also neutralizes its target effectively suggesting its potential use as topical therapy for AD.

Development and characterization of a 3D in vitro model mimicking acneic skin.

Acne is an inflammatory skin disease of the pilosebaceous unit, involving four essential factors: hyperseborrhoea combined to a modification of sebum composition, colonization by Cutibacterium (C.) acnes, hyperkeratinization and secreted inflammation. Understanding and mimicking compromised skin is essential to further develop appropriate therapeutic solutions. This study aimed to develop new in vitro 3D models mimicking acneic skin, by combining two main factors involved in the physiopathology, namely, altered sebum composition and C. acnes invasion. Normal human keratinocytes were first used to generate reconstructed human epidermis (RHE) that were then left untreated (control) or treated topically with a combination of both peroxidized squalene and C. acnes cultures. Once validated, this model considered relevant to mimic acneic skin, was further improved by using different phylotypes of C. acnes strains specifically isolated from healthy and acneic patients. While both phylotypes IB and II did not significantly alter RHE, C. acnes IA1 strains induce major acneic skin hallmarks such as hyperkeratinization, secreted inflammation and altered barrier function. Interestingly, these results are obtained independently of the origin of IA1 phylotypes (acneic vs. healthy patient), thus suggesting a role of the ecosystem in controlling C. acnes virulence in healthy skin. In conclusion, by combining two major factors involved in the physiopathology of acne, we (1) succeeded to design in vitro 3D models mimicking this skin disorder and (2) highlighted how C. acnes phylotypes can have an impact on epidermal physiology. These relevant models will be suitable for the substantiation of therapeutic molecules dedicated to acne treatment.

Immunotherapies in cutaneous pathologies: an overview.

Skin is a vital protective organ, the main role of which is to provide a physical barrier and to prevent the entry of pathogens. Various pathologies, such as atopic dermatitis (AD), psoriasis (PSO), or skin cancers, can affect the skin, and all show a high and increasing prevalence. Many antibodies are currently used in the treatment of these diseases. However, various studies are underway for the development of new biologics directed against specific targets. In this review, we describe current biologics used in skin pathologies as well as antibodies in development. We also discuss various immunotherapy examples that use new delivery technologies, such as microneedle patch, nanoparticles (NPs), liposomes, or gel formulation.