کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5818066 | 1557322 | 2016 | 20 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Nanostructured lipid carrier mediates effective delivery of methotrexate to induce apoptosis of rheumatoid arthritis via NF-κB and FOXO1 Nanostructured lipid carrier mediates effective delivery of methotrexate to induce apoptosis of rheumatoid arthritis via NF-κB and FOXO1](/preview/png/5818066.png)
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 methotrexate (MTX). The prepared NLCs were optimized with different preparative variables such as particle size <200 nm, poly-dispersity index (PDI) <0.2, and entrapment efficiency â¼85%. 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 8 h followed by sustained release (up to 85%) by the end of 48th h. NLCs showed greater uptake in human 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-κB-IkB and FOXO1 is supported by fold regulations calculated for various apoptotic and pro-inflammatory biomarkers carried out by RT-PCR. The immunocytochemistry to detect IL-6 expression and immunofluorescence assay suggested that induced apoptosis occurs in experimentally induced in vitro arthritis model treated with NLCs-MTX. We saw reduced inflammation and triggered apoptosis through NF-κB & FOXO1 pathways induced by MTX 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.
Graphical Abstract148
Journal: International Journal of Pharmaceutics - Volume 499, Issues 1â2, 29 February 2016, Pages 301-320