Liposomes as possible carriers for lactoferrin in the local treatment of inflammatory diseases

Liposomes prepared from naturally occurring biodegradable and nontoxic lipi ds are good candidates for local delivery of therapeutic agents. Treatment of arthritis by intra-articular administration of anti-inflammatory drugs e ncapsulated in liposomes prolongs the residence time of the drug in the joi nt. We have previously shown that intra-articular injection of human lactof errin (hLf), a glycoprotein that possesses anti-inflammatory and antimicrob ial activities, into mice with collagen-induced arthritis reduces inflammat ion. We have now investigated the possibility of using liposome-entrapped h Lf as a delivery system to prolong hLf retention at sites of local inflamma tion such as the rheumatoid joint. Entrapment of hLf in negatively charged liposomes enhanced its accumulation in cultured human synovial fibroblasts from rheumatoid arthritis (RA) patients, compared with positively charged f ormulations or free protein. However, in the presence of synovial fluid, po sitively charged liposomes with entrapped hLf were more stable than the neg atively charged formulations. In vivo experiments in mice with collagen-ind uced arthritis showed that the positive liposomes were more efficient in pr olonging the residence time of hLf in the inflamed joint as compared with o ther liposomes, Thus, the amount of hLf retained in the joint after 2 hr wa s 60% of the injected dose in the case of positive liposomes and only 16% f or negative pH-sensitive liposomes, The results suggest that entrapment of hLf in positively charged liposomes may modify its pharmacodynamic profile and be of therapeutic benefit in the treatment of RA and other local inflam matory conditions.