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

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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-glycero3-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 levels in serum samples. This study suggests feasibility of using surface-active phospholipid based carriers for local, intra-articular therapy of paclitaxel in arthritis.
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Keywords: ANTIGEN-INDUCED ARTHRITIS; INFLAMMATION; INTRA-ARTICULAR; LIPOSOMES; PACLITAXEL; TNFα

Document Type: Research Article

Publication date: July 1, 2015

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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