Publication Database

Core-multishell-nanocarrier for topical drug delivery in a psoriasis mouse model (2018)

Art

Hochschulschrift

Autor

Pischon, Jeanette Hannah Charlotte (WE 12)

Quelle

Berlin: Mensch und Buch Verlag Berlin, 2018 — VII, 64 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/23577

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Psoriasis is a common, chronic, multifactorial, human skin disease, characterized by well-demarcated, raised, erythematous plaques covered with silvery scales. It is incurable and often requires long period therapy with immunomodulatory drugs, which can lead to side effects, especially when administered systemically in more severe cases. Nanocarrier are engineered particles of a size between 1 nm and 100 nm at least in one dimension. For skin, nanocarrier are designed to increase the delivery of drugs or genes through the skin barrier, target the drug to a specific layer, or prevent systemic distribution and thereby negative effects in distant organs. In paper 1 of this thesis, core-multishell nanocarrier were investigated topically on mouse skin in vivo. This nanocarrier had been designed like a uni-molecular micelle with a hydrophilic core, an inner lipophilic shell, and an outer hydrophilic shell to make the particle water-soluble and provide space for drugs of different lipophilicity to be loaded into the core or the inner shell. Originally, they had been thought to penetrate through the skin and release their cargo at its site of action. Literature already had stated that several nanocarrier or nanoparticles do not penetrate into skin, whereas others do and even others penetrate only through a disrupted barrier. The core-multishell nanocarrier used here did not penetrate into viable layers of intact or inflamed skin using the imiquimod-induced psoriasis model in BALB/c mice. Instead, they accumulated in the stratum corneum. Previous in vitro data had shown core-multishell nanocarrier penetration into tape stripped human skin ex vivo. The accumulation in the stratum corneum could possibly be used as a depot for a retarded and prolonged release of drugs. Parallel to the penetration study no adverse effects were observed locally or systemically. This is in concordance with literature also stating no negative effects even after repeated subcutaneous injection of this carrier. The topical application of nile red loaded core-multishell nanocarrier revealed superior cargo delivery into the viable epidermis compared to a nile red cream. Further elucidation of the mechanism by which the core-multishell nanocarrier enhances the penetration of nile red, and proof of concept for real drugs are needed. However, the core-multishell nanocarrier remains as a promising candidate for further development for therapy of skin diseases including testing of a therapeutic surplus value of drug loaded nanocarrier compared to commercial topical drug formulations. No tacrolimus-specific anti-inflammatory effects could be shown in the imiquimod-induced psoriasis-like dermatitis model using BALB/c mice, despite penetration of the drug into the dermis. Further research is needed to elucidate the reason for the lack of that efficacy and the conflict to literature and the dependence of tacrolimus efficacy in this model on mouse strains. However, this model was not applicable to evaluate therapeutic superiority of core-multishell nanocarrier for tacrolimus delivery compared to tacrolimus ointment. The importance of choosing an appropriate model for the specific question, using multiple objective readout parameters to avoid over-interpretation of small variations, and testing against all needed control groups, including a vehicle control, in addition to untreated controls, is highlighted.