Background/Purpose: MM-II is a dispersion of large, empty multilamellar liposomes for intraarticular (IA) injection that reduced knee pain in osteoarthritic patients for up to 26 weeks in a global clinical study (NCT04506463). Previous studies showed these liposomes coat cartilage and menisci under compression, providing lubrication and reducing wear. After injection, most liposomes are absorbed and metabolized by joint tissues, while some adhere to knee surfaces to maintain lubrication. This study aimed to characterize MM-II clearance and its association with knee components in healthy rats.

Methods: Sulfo-Cyanin 5.5–labelled MM-II (Cy5.5-MM-II) liposomes were produced from dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC), and Sulfo-Cy5.5-phosphatidylethanolamine at a molar ratio of 0.5445:0.4550:0.0005. Male Wistar rats (N&#3f8) received bilateral IA injections of Cy5.5-MM-II (3.2 mg per knee) on day 0 and were imaged with an IVIS Lumina LT on days 0, 1, 4, 6, 14, and 28 to measure radiant efficiency, with a non-injected rat as a background control. On day 28, knees from N&#3f3 Cy5.5-MM-II injected rats were excised, soft tissues removed, and components (femur head, tibia plateau, patella, menisci) isolated for scanning. Regions of interest (ROIs) were defined in cartilage areas to normalize fluorescence signals. Additional knees were decalcified, stained with DAPI, cryosectioned, and analyzed via fluorescent microscopy.

Results: MM-II clearance showed an initial exponential phase (half-life ~3 days) for 11 days, followed by a terminal phase where approximately 3% of the dose remained through day 28 (Figure 1A). Ex vivo imaging and histology at day 28 (Figure 1B, C) confirmed similar liposome distribution in femur, tibia, and patella cartilage, with retention also observed in the menisci.

Conclusion: IA injection in rat knees led to most MM-II liposomes clearing within 1–2 weeks, while a fraction persisted on cartilage and menisci for at least 28 days, supporting clinical findings of prolonged knee pain relief.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clearance-kinetics-and-cartilage-retention-of-mm-ii-a-dispersion-of-large-empty-liposomes-in-rat-knees/