UNASSIGNED: Present study was designed to develop novel nano-structured lipid carriers (NLCs) formulated by lipid mixture and chemical permeation enhancer-based hydrogel for an effective transdermal delivery of @entity1499 ( @entity6822 ). The prepared NLCs were optimized with different preparative variables such as particle size <200nm, poly-dispersity index (PDI) <0.2, and entrapment efficiency    85%. The drug incorporated into NLCs-gel base showed excellent spread ability without any grittiness during rheological behavior and texture profile analysis. The in vitro release showed biphasic release pattern with initial fast release of drug (>50%) in 8h followed by sustained release (up to 85%) by the end of 48thh. NLCs showed greater uptake in @entity1 hyper-proliferative keratinocyte cell line (HaCaT). NLCs showed increased expression of inflammatory mediators as well asapoptosis in U937 monocytic cells. The greater expression of pro-apoptotic gene Bim regulated by NF-kB-IkB and @entity4012 is supported by fold regulations calculated for various apoptotic and pro-inflammatory biomarkers carried out by RT-PCR. The immunocytochemistry to detect @entity650 expression and immunofluorescence assay suggested that induced apoptosis occurs in experimentally induced in vitro @entity625 model treated with NLCs- @entity6822 . We saw reduced @entity32 and triggered apoptosis through NF-kB _ @entity4012 pathways induced by @entity6822 loaded NLCs in rheumatoid arthritic cells. In addition, formulated NLCs exhibit better skin permeation with higher permeation flux _ enhancement ratio as shown by confocal laser scanning microscopy (CLSM). Moreover, histopathological examinations of skin are suggestive of safety potential of NLCs.

Nanostructured lipid carrier mediates effective delivery of @entity1499 to induce apoptosis of rheumatoid arthritis via NF-kB and XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity650 :: ('3569', 'Gene') :: ['IL-6'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity625 :: ('MESH:D001168', 'Disease') :: ['arthritis'] @entity6822 :: ('D008727', 'Chemical') :: ['MTX'] @entity4012 :: ('2308', 'Gene') :: ['FOXO1'] @entity1499 :: ('MESH:D008727', 'Chemical') :: ['methotrexate']
@entity4012 :: (2308,Gene) :: ['FOXO1']
