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

Abstract

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 TNFα 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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“…Paclitaxel, an antineoplastic drug used in cancer chemotherapy, interferes with several processes involved with inflammatory arthritis such as angiogenesis and collagenase expression but its use is limited mainly due to systemic toxicity. To overcome such limitations, Paclitaxel, in combination with phospholipid mimetic nanocarrier system is used as an intra-articular injection in rat joints results in significant improvement in gait scores and inflammation in synovial joints, with a confirmed reduction in TNFα levels [ 32 ]. Phospholipid nanocarrier system was prepared using dipalmitoyl-sn-glycero3-phosphotidylcholine (DPPC) prepared using a thin film hydration method with a size of 311 ± 57 nm and 92 ± 0.6% paclitaxel encapsulated with short initial burst phase and sustained release profile with a cumulative release of 18 ± 0.36% [ 32 ].…”

“…To overcome such limitations, Paclitaxel, in combination with phospholipid mimetic nanocarrier system is used as an intra-articular injection in rat joints results in significant improvement in gait scores and inflammation in synovial joints, with a confirmed reduction in TNFα levels [ 32 ]. Phospholipid nanocarrier system was prepared using dipalmitoyl-sn-glycero3-phosphotidylcholine (DPPC) prepared using a thin film hydration method with a size of 311 ± 57 nm and 92 ± 0.6% paclitaxel encapsulated with short initial burst phase and sustained release profile with a cumulative release of 18 ± 0.36% [ 32 ]. Thymol, a natural-synthetic compound, has several benefits associated with it such as being antibacterial, antiseptic, and antioxidant but they decompose easily.…”