title: Dermal drug delivery with drug nanocrystals: hair follicle targeting, passive penetration and the novel method for their determination
title: Wirkstoff-Nanokristalle zur dermaßen Applikation: Haarfollikel-Targeting, passive Penetration und die neue Methode zur deren Bestimmung
titleType: AlternativeTitle
Creators: name: Pelikh, Olga
Publisher: name: Philipps-Universität Marburg
Year: 2021
Subjects: dermale Wirkstoffabgabe
dermal drug delivery
dermale Nanokristalle
passive Penetration
dermal nanocrystals
image analysis
drug nanocrystals
ImageJ
passive penetration
dermale Wirkstoffapplikation
hair follicle targeting
digitale Bildanalyse
dermal penetration
Haarfollikeltargeting
Technology (Applied sciences)
Technik

description: In this thesis, drug nanocrystals (NC) as a formulation approach for poorly soluble active compounds (AC) for the follicular and passive dermal penetration were systematically investigated. This thesis aimed to establish the optimum method for the determination of the follicular and passive dermal penetration efficacy of NC formulations and using this method to investigate the influences of essential formulation aspects on the penetration efficacy of NC formulations into the hair follicles and into the skin. The previously established “universal” method for characterization of the follicular and the passive dermal penetration efficacy of dermal formulations - differential skin stripping - was found to be insufficient to characterize the follicular and dermal uptake of dermal NC formulations. Thus, a novel “two-in-one” method for sound characterization of follicular and passive dermal penetration of NC formulations was established. The novel method is based on the visualization of the penetration of the AC into the hair follicles and into the skin using fluorescence microscopy. The quantification of the follicular penetration is carried out by measuring the penetration depth of NC in µm directly from fluorescence images, whereas for quantification of the passive dermal penetration, a method for digital image analysis with the software ImageJ was established in this thesis. The novel method represents the unique “two-in-one” technique allowing for investigation of the follicular and the passive dermal penetration of one formulation using only one method, one skin penetration model and within the skin penetration model only one skin area. The novel method provides a detailed time and space resolved determination of the penetration fate of a dermal formulation. With this, it represents a sound, reliable and universal tool for smart characterization of the follicular and passive dermal penetration of dermal formulations that overcomes all substantial disadvantages of conventional methods and provides optimized solutions. Thus, from now on, a new chapter in penetration experiments with dermal formulations begins. Using the novel method, the influences of essential formulation aspects on the follicular and passive dermal penetration of NC formulations were detailed and mechanistically investigated. Based on the outcome of these investigations, from now on, by tailored optimization of formulation components, tailor-made NC formulations for effective hair follicle targeting, effective passive dermal penetration and targeted dermal drug delivery can be “designed”. This approach – tailored optimization of NC formulations by formulation components – should now be realized in the development of highly effective dermal products with the drug NC, that would for sure enter the market in the next years.