Poly-phosphocholination of liposomes leads to highly-extended retention time in mice joints

Surface-attached layers of phosphatidylcholine (PC) lipid vesicles (liposomes) may reduce the friction coefficient μ (= force-to-slide/load) between the sliding surfaces down to μ ≈ 10⁻³–10⁻⁴ up to tens of atm contact pressures, as high as those in the major joints (hips or knees). Such friction reduction is attributed to hydration lubrication by the highly-hydrated phosphocholine head-groups exposed at the outer vesicle surfaces. It has been suggested therefore that intra-articular (IA) administration of liposomes as potential boundary lubricants may alleviate degenerative, friction-associated joint conditions such as osteoarthritis (OA), which is associated with insufficient lubrication at the articular cartilage surface. To overcome the problem, common to all nanoparticles, of rapid removal by the mononuclear phagocyte system, as well as to ensure long-term colloidal stability during storage, functionalizing liposomes with poly(ethylene glycol) moieties, PEGylation, is often used. Here we describe a different liposome functionalization approach, using poly(2-methacryloyloxyethyl phosphorylcholine), PMPC, moieties (strictly, lipid–PMPC conjugates), and compare the retention time in mice joints of such PMPCylated liposomes with otherwise-identical but PEGylated vesicles following IA administration. We find, using fluorescence labeling and in vivo optical imaging, that when PMPC-stabilized liposomes are injected into mice knee joints, there is a massive increase of the vesicles’ retention half-life in the joints of about (4–5)-fold (ca. 300–400% increase in retention time) compared with the PEGylated liposomes (and some 100-fold longer than the retention time of intra-articularly injected hyaluronan or HA). Such PMPCylated liposomes are therefore promising candidates as potential long-lived boundary lubricants at the articular cartilage surface, with implication for friction-associated pathologies. Moreover, as lipid vesicles are well known to be efficient drug carriers, such long retention in the joints may enable analgesic or anti-inflammatory agents for joint pathologies to be more efficiently delivered via IA administration using PMPCylated liposomal vehicles relative to PEGylated ones.