Biodegradable core-multishell nanocarrier: topical tacrolimus delivery for treatment of dermatitis
- 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 liverTwo 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.…
Author details: | Moritz Jan Florian RadbruchGND, Jeanette Hannah Charlotte PischonGND, Fang DuGND, Rainer HaagORCiDGND, Fabian SchumacherORCiDGND, Burkhard KleuserORCiDGND, Lars MundhenkGND, Achim GruberGND |
---|---|
DOI: | https://doi.org/10.1016/j.jconrel.2022.07.025 |
ISSN: | 0168-3659 |
ISSN: | 1873-4995 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/35905785 |
Title of parent work (English): | Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems |
Publisher: | Elsevier |
Place of publishing: | New York, NY [u.a.] |
Publication type: | Article |
Language: | English |
Date of first publication: | 2022/08/08 |
Publication year: | 2022 |
Release date: | 2024/08/22 |
Tag: | core-multishell (CMS) nanocarriers; dermal drug administration; drug delivery systems; penetration enhancement; tacrolimus; topical drug delivery |
Volume: | 349 |
Number of pages: | 12 |
First page: | 917 |
Last Page: | 928 |
Funding institution: | German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Peer review: | Referiert |
License (German): | Keine öffentliche Lizenz: Unter Urheberrechtsschutz |