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Joint Surface-Active Phospholipid-Mimetic Liposomes for Intra-Articular Delivery of Paclitaxel

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Title Joint Surface-Active Phospholipid-Mimetic Liposomes for Intra-Articular Delivery of Paclitaxel
 
Creator DYONDI, D
SARKAR, A
BANERJEE, R
 
Subject COLLAGEN-INDUCED ARTHRITIS
ANTIGEN-INDUCED ARTHRITIS
RHEUMATOID-ARTHRITIS
IN-VITRO
MICROSPHERE FORMULATIONS
BOUNDARY LUBRICATION
ARTICULAR-CARTILAGE
SYNOVIAL JOINTS
VIVO EVALUATION
METHOTREXATE
Paclitaxel
Intra-Articular
Liposomes
Inflammation
TNF alpha
Antigen-Induced Arthritis
 
Description Synovial inflammation, angiogenesis and joint degradation are the hallmarks of inflammatory arthritis progression. Angiostatic targeting is an extensively studied potential therapeutic option for inflammatory arthritis,. Studies have confirmed that surface-active phospholipids (SAPLs), predominantly phosphatidylcholines (PCs), are responsible for the lubricating properties of lubricin in joints. Paclitaxel, a potent antineoplastic agent in cancer chemotherapy, has been shown to inhibit several processes associated with arthritis development such as angiogenesis, neutrophil activation and collagenase expression but is limited by systemic toxicity. This study was aimed at designing a surface-active phospholipid mimetic nanocarrier system and assessing its efficacy for intra-articular delivery of paclitaxel in rat joints. Dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) liposomes were prepared using a thin-film hydration method and characterized for size, morphology, drug encapsulation and in vitro release. DPPC liposomes of a size of 311 +/- 57 nm and 92 +/- 0.6% paclitaxel encapsulation were developed. In vitro release studies showed a short initial burst phase and a sustained release profile with a cumulative release of 18 +/- 0.36% of the drug by 60 h in phosphate-buffered saline (PBS). The efficacy of the intra-articular formulation was evaluated in antigen-induced arthritic rat models and compared with direct injections of paclitaxel. After a 28-day period, intra-articular paclitaxel delivered in liposomes led to a significant improvement in gait scores and synovial inflammation in rats compared to the control, as seen in histopathology studies. Reduction in inflammation in the experimental group was confirmed by evaluating TNF alpha levels in serum samples. This study suggests feasibility of using surface-active phospholipid based carriers for local, intra-articular therapy of paclitaxel in arthritis.
 
Publisher AMER SCIENTIFIC PUBLISHERS
 
Date 2016-01-15T10:00:44Z
2016-01-15T10:00:44Z
2015
 
Type Article
 
Identifier JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, 11(7)1225-1235
1550-7033
1550-7041
http://dx.doi.org/10.1166/jbn.2015.2061
http://dspace.library.iitb.ac.in/jspui/handle/100/18316
 
Language en