The use of anti-COX2 siRNA coated onto PLGA nanoparticles loading dexamethasone in the treatment of rheumatoid arthritis.
In drug delivery systems, some genes have the potential to interrupt unnecessary gene expression in specific target cells. In this study, two types of drug, glucocorticoids and siRNA, were co-delivered into conditioned cells to inhibit the expression of unnecessary genes and proteins involved in arthritis. To deliver the two factors into a human chondrocyte cell line (C28/I2), dexamethasone was first loaded into PLGA nanoparticles, and then drug-loaded PLGA nanoparticles were complexed with poly(ethyleneimine) (PEI)/siRNA. To test the co-delivery of siRNA and dexamethasone into chondrocytes, cells were transfected with green fluorescence protein siRNA (GFP siRNA) and drugs. After transfection with GFP siRNA, 70% reduction of C28/I2 cells demonstrated GFP expression, whereas MOCK carrying PLGA nanoparticles and PLGA nanoparticles without siRNA showed no differences of GFP expressions. COX-2 and iNOS productions in C28/I2 cells were examined after TNF-α pre-treatment to induce expression of arthritis-related molecules in vitro. The reduction of gene and protein expression associated with arthritis by transfection with dexamethasone-loaded and COX-2 siRNA-complexed PLGA nanoparticles was evaluated by RT-PCR, real time-qPCR, immunoblotting, immunohistochemistry, and immunofluorescence imaging.
Department of Biomedical Science, College of Life Science, CHA University, 3F, Yatap Acecore, 502 Yatap-dong Bundang-gu, Seongnam-si, Republic of Korea.
Ji Sun
JS
Park
Han Na
HN
Yang
Su Yeon
SY
Jeon
Dae Gyun
DG
Woo
Moon Suk
MS
Kim
Keun-Hong
KH
Park
D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D003907:Dexamethasone / Q000737:chemistry* / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D053583:Interleukin-1beta; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D053148:Caspase 3