Enhanced uptake and anti-maturation effect of celastrol-loaded mannosylated liposomes on dendritic cells for psoriasis treatment

Psoriasis is an autoimmune skin disease in which dendritic cells(DCs) trigger the progression of psoriasis by complex interactions with keratinocytes and other immune cells. In the present study,we aimed to load celastrol, an anti-inflammatory ingredient isolated from Chinese herbs, on mannosylated liposomes to enhance DC uptake as well as to induce DC tolerance in an imiquimod-induced psoriasis-like mouse model. Mannose was grafted onto liposomes to target mannose receptors on DCs. The results demonstrated that compared with unmodified liposomes, DCs preferred to take up more fluorescence-labeled mannosylated liposomes. After loading celastrol into mannose-modified liposomes,they effectively inhibited the expression of maturation markers, including CD80, CD86 and MHC-II, on DCs both in vitro and in vivo. Additionally, after intradermal injection with a microneedle, celastrolloaded mannose-modified liposomes(CEL-MAN-LPs) achieved a superior therapeutic effect compared with free drug and celastrol-loaded unmodified liposomes in the psoriasis mouse model in terms of the psoriasis area and severity index, histology evaluation, spleen weight, and expression of inflammatory cytokines. In conclusion, our results clearly revealed that CEL-MAN-LPs was an effective formulation for psoriasis treatment and suggested that this treatment has the potential to be applied to other inflammatory diseases triggered by activated DCs.

Uptake and traffcking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model

Psoriasis is an autoimmune infammatory disease,where dendritic cells(DCs)play an important role in its pathogenesis.In our previous work,we have demonstrated that topical delivery of curcumin-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles(NPs)could treat Imiquimod(IMQ)-induced psoriasis-like mice.The objective of this study is to further elucidate biofate of PLGA NPs after intradermal delivery including DCs uptake,and their further traffcking in psoriasis-like mice model by using fuorescence probes.Two-sized DiO/DiI-loaded PLGA NPs of 50±4.9 nm(S-NPs)and 226±7.8 nm(L-NPs)were fabricated,respectively.In vitro cellular uptake results showed that NPs could be internalized into DCs with intact form,and DCs preferred to uptake larger NPs.Consistently,in vivo study showed that L-NPs were more captured by DCs and NPs were frstly transported to skindraining lymph nodes(SDLN),then to spleens after 8 h injection,whereas more S-NPs were transported into SDLN and spleens.Moreover,FRET imaging showed more structurally intact L-NPs distributed in skins and lymph nodes.In conclusion,particle size can affect the uptake and traffcking of NPs by DCs in skin and lymphoid system,which needs to be considered in NPs tailing to treat infammatory skin disease like psoriasis.