@article{RadbruchPischonDuetal.2022,
  author    = {Radbruch, Moritz Jan Florian and Pischon, Jeanette Hannah Charlotte and Du, Fang and Haag, Rainer and Schumacher, Fabian and Kleuser, Burkhard and Mundhenk, Lars and Gruber, Achim},
  title     = {Biodegradable core-multishell nanocarrier: topical tacrolimus delivery for treatment of dermatitis},
  series = {Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems},
  volume    = {349},
  journal   = {Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems},
  publisher = {Elsevier},
  address   = {New York, NY [u.a.]},
  issn      = {0168-3659},
  doi       = {10.1016/j.jconrel.2022.07.025},
  pages     = {917 -- 928},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}