To improve the treatment of psoriasiform inflammation, we developed actively targeted nanocarriers loaded with the phosphodiesterase 4 inhibitor AN2728. Methods: Phospholipid-poly(lactic-co-glycolic acid) nanohybrids were prepared and conjugated with monovalent anti-desmoglein 3 antibody to bind keratinocytes. Results: The actively targeted nanohybrids were 229 nm in mean size with a nearly neutral surface charge. Flow cytometry and confocal microscopy showed a 9-fold increase in keratinocyte uptake of targeted nanohybrids relative to non-targeted nanoparticles. The nanoparticles localized mainly in lysosomes after internalization. AN2728-loaded antibody-conjugated nanocarriers inhibited cytokine/chemokine overexpression in activated keratinocytes without affecting cell viability. The targeted nanohybrids also suppressed neutrophil migration by reducing CXCL1 and CXCL2 release from keratinocytes. Following subcutaneous administration in mice, the nanohybrids distributed to the epidermis and hair follicles. In a psoriasis-like skin mouse model, the actively targeted nanoparticles were superior to free drug and non-targeted nanoparticles in mitigating skin inflammation. Intervention with the targeted nanosystem reduced the epidermal thickness of the psoriasiform lesion from 191 to 42 µm, decreased the Psoriasis Area Severity Index by 74%, restored barrier function, and returned chemokine levels to baseline. Conclusions: Our developed nanosystem was safe and demonstrated efficient targeting properties for the treatment of cutaneous inflammation.
- MeSH
- bicyklické sloučeniny heterocyklické aplikace a dávkování farmakologie MeSH
- buněčné linie keratinocytů HaCaT MeSH
- chemokin CXCL1 účinky léků imunologie MeSH
- chemokin CXCL2 účinky léků imunologie MeSH
- chemotaxe účinky léků MeSH
- desmoglein 3 imunologie MeSH
- epidermis MeSH
- fosfolipidy * MeSH
- imunokonjugáty farmakologie MeSH
- inhibitory fosfodiesterasy 4 aplikace a dávkování farmakologie MeSH
- keratinocyty účinky léků imunologie MeSH
- kopolymer kyseliny glykolové a mléčné * MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- lyzozomy metabolismus ultrastruktura MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nanočástice * MeSH
- neutrofily účinky léků MeSH
- nosiče léků MeSH
- protilátky imunologie MeSH
- psoriáza imunologie patologie MeSH
- sloučeniny boru aplikace a dávkování farmakologie MeSH
- vlasový folikul MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
