TY  - JOUR
A1  - Radbruch, Moritz Jan Florian
A1  - Pischon, Jeanette Hannah Charlotte
A1  - Du, Fang
A1  - Haag, Rainer
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Mundhenk, Lars
A1  - Gruber, Achim
T1  - Biodegradable core-multishell nanocarrier: topical tacrolimus delivery for treatment of dermatitis
JF  - Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems
N2  - 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.
KW  - drug delivery systems
KW  - core-multishell (CMS) nanocarriers
KW  - tacrolimus
KW  - topical drug delivery
KW  - dermal drug administration
KW  - penetration enhancement
Y1  - 2022
U6  - https://doi.org/10.1016/j.jconrel.2022.07.025
SN  - 0168-3659
SN  - 1873-4995
VL  - 349
SP  - 917
EP  - 928
PB  - Elsevier
CY  - New York, NY [u.a.]
ER  -