title: Targeted delivery of low-dose dexamethasone using PCL-PEG micelles for effective treatment of rheumatoid arthritis.
abstract: Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block-poly (ε-caprolactone) (PCL-PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL-PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL-PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: xunsun22@gmail.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015926:Complement C3a / Q000378:metabolism; D003374:Coumarins / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006614:Hindlimb / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007596:Joints / Q000378:metabolism / Q000473:pathology; D007783:Lactones / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008823:Micelles; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D000067996:RAW 264.7 Cells; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D053583:Interleukin-1beta; D007783:Lactones; D008823:Micelles; D014409:Tumor Necrosis Factor-alpha; C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; D003907:Dexamethasone; D015926:Complement C3a; C030123:coumarin
keywords: Dexamethasone; PCL–PEG; Rheumatoid arthritis; Side effect