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Owing their unique chemical and physical properties core-multishell (CMS) nanocarriers are thought to underlie their exploitable biomedical use for a topical treatment of skin diseases. This highlights the need to consider not only the efficacy of CMS nanocarriers but also the potentially unpredictable and adverse consequences of their exposure thereto. As CMS nanocarriers are able to penetrate into viable layers of normal and stripped human skin ex vivo as well as in in vitro skin disease models the understanding of nanoparticle crosstalk with components of the immune system requires thorough investigation. Our studies highlight the biocompatible properties of CMS nanocarriers on Langerhans cells of the skin as they did neither induce cytotoxicity and genotoxicity nor cause reactive oxygen species (ROS) or an immunological response. Nevertheless, CMS nanocarriers were efficiently taken up by Langerhans cells via divergent endocytic pathways. Bioimaging of CMS nanocarriers by fluorescence lifetime imaging microscopy (FLIM) and flow cytometry indicated not only a localization within the lysosomes but also an energy-dependent exocytosis of unmodified CMS nanocarriers into the extracellular environment. (C) 2018 Elsevier Ltd. All rights reserved.
Biodegradable core-multishell nanocarrier: topical tacrolimus delivery for treatment of dermatitis
(2022)
Two challenges in topical drug delivery to the skin include solubilizing hydrophobic drugs in water-based formulations and increasing drug penetration into the skin. Polymeric core-multishell nanocarrier (CMS), particularly the novel biodegradable CMS (bCMS = hPG-PCL1.1K-mPEG(2k)-CMS) have shown both advantages on excised skin ex vivo.
Here, we investigated topical delivery of tacrolimus (TAC; > 500 g/mol) by bCMS in a hydrogel on an oxazolone-induced model of dermatitis in vivo. As expected, bCMS successfully delivered TAC into the skin.
However, in vivo they did not increase, but decrease TAC penetration through the stratum corneum compared to ointment.
Differences in the resulting mean concentrations were mostly non-significant in the skin (epidermis: 35.7 +/- 20.9 ng/cm(2) for bCMS vs. 92.6 +/- 62.7 ng/cm(2) for ointment; dermis: 76.8 +/- 26.8 ng/cm(2) vs 118.2 +/- 50.4 ng/cm(2)), but highly significant in blood (plasma: 1.1 +/- 0.4 ng/ml vs 11.3 +/- 9.3 ng/ml; erythrocytes: 0.5 +/- 0.2 ng/ml vs 3.4 +/- 2.4 ng/ml) and liver (0.01 +/- 0.01 ng/mg vs 0.03 +/- 0.01 ng/mg). bCMS were detected in the stratum corneum but not in viable skin or beyond.
The therapeutic efficacy of TAC delivered by bCMS was equivalent to that of standard TAC ointment.
Our results suggest that bCMS may be a promising carrier for the topical delivery of TAC. The quantitative difference to previous results should be interpreted in light of structural differences between murine and human skin, but highlights the need as well as potential methods to develop more a complex ex vivo analysis on human skin to ensure quantitative predictive value.