1803: Patching of Damaged Meniscus and Cartilage of Osteoarthritic Animals by MM-II, a Dispersion of Empty Large Multilamellar Liposomes

Background/Purpose: Cartilage wear in knee osteoarthritis (KOA) is linked to reduced boundary lubrication. Occasionally, the meniscus also wears out in KOA, potentially accelerating the disease. MM-II is a dispersion of empty, large multilamellar liposomes for intraarticular (IA) injection. A single injection of MM-II has reduced knee pain for up to 26 weeks in a global clinical study (NCT04506463). MM-II was shown to coat cartilage and menisci and to reduce cartilage degeneration in surgically induced KOA models. The current study aimed to assess interaction of MM-II with cartilage and menisci in monosodium-iodoacetate KOA rat model in which cartilage pathology is reminiscent of human KOA.

Methods: Osteoarthritis was induced by 0.6mg monoiodoacetate (MIA) IA injection in rats. At 14 days post MIA injection, fluorescently labelled MM-II liposomes were bilaterally IA injected. Knees were harvested at 1-week post-injection, fixed, decalcified in EDTA, frozen, cryosectioned, stained with DAPI and visualized by fluorescent microscopy. Animal procedures were approved by the local ethics committee and relevant authorities.

Results: In MIA-treated knees, accumulation of MM-II was seen one week post administration specifically in regions with extensive cell death in both cartilage and meniscus. In contrast, in flanking regions with live cells or in healthy knees, MM-II was shown to coat cartilage and meniscus with fine layer as seen previously in surgically induced KOA models.

Conclusion: Pending on the KOA model, MM-II liposomes coat or patch OA cartilage and menisci. These observations, together with previous ones showing lubrication by MM-II, suggest a novel mechanism that may underlies MM-II clinical benefit in KOA.