Liposomes as Possible Carriers for Lactoferrin in the Local Treatment of Inflammatory Diseases

Abstract

Liposomes prepared from naturally occurring biodegradable and nontoxic lipids are good candidates for local delivery of therapeutic agents. Treatment of arthritis by intra-articular administration of anti-inflammatory drugs encapsulated in liposomes prolongs the residence time of the drug in the joint. We have previously shown that intra-articular injection of human lactoferrin (hLf), a glycoprotein that possesses anti-inflammatory and antimicrobial activities, into mice with collagen-induced arthritis reduces inflammation. We have now investigated the possibility of using liposome-entrapped hLf as a delivery system to prolong hLf retention at sites of local inflammation 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 formulations or free protein. However, in the presence of synovial fluid, positively charged liposomes with entrapped hLf were more stable than the negatively charged formulations. In vivo experiments in mice with collagen-induced arthritis showed that the positive liposomes were more efficient in prolonging the residence time of hLf in the inflamed joint as compared with other liposomes. Thus, the amount of hLf retained in the joint after 2 hr was 60% of the injected dose in the case of positive liposomes and only 16% for 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 inflammatory conditions.

Inhibitory effects of orally administrated liposomal bovine lactoferrin on the LPS-induced osteoclastogenesis

“…Recently, liposomalization of bLF was shown to improve resistance of bLF to gastric digestion, suggesting that oral administration of L-bLF could be a novel active constituent useful for preventive and therapeutic treatment of inflammatory diseases. [20][21][22] Expectedly, oral administration of L-bLF exhibited more stable and effective suppression in the increase of osteoclasts and preosteoclasts than bLF in our animal model. These results suggest that intact bLF absorbed from intestinal mucosa may be important for its inhibitory effects.…”

“…Liposomalization of bLF has been shown to enhance the anti-inflammatory effects of bLF. 20,21 Therefore, we stabilized bLF by liposomalization 22 to enhance its absorbability from the intestinal lumen and transport into the blood circulation.…”

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

“…However, the first reports of liposomes as drug carriers appeared in the 1970s and there are still few results reported on liposomes for intra-articular application. In 2001, Trif et al reported a positive effect of human Lactoferrin encapsulated in liposomes in collagen-induced arthritis in mice [91]. Elron-Gross et al reported a reduction of inflammation in a monosodium iodoacetate (MIA) induced OA rat knee after a liposomal dexamethasone and diclofenac combination injection as compared to control assessed by MRI, in 2009 [32,92], and Dong et al found a combination of Cxb incorporated liposomes and HA to be more effective in pain control and cartilage protection than a single Cxb injection, Cxb liposome, and HA treatment alone [93].…”

Healthy Multifunctional Spectra of Milk Glycoproteins and Their Fragments – a Review Article

“…As a result, interaction of LPS with receptors is disrupted and downstream events such as upregulation of infl ammatory cytokines are reduced [Baveye et al, 1999]. Another potential anti-infl ammatory role of LF is through the sequestration of "free" iron at infl ammatory foci, such as rheumatoid joints, thus preventing catalysis of the production of damaging free radicals [Trif et al, 2001 andGuillen et al, 2000]. LF can also reduce cutaneous infl ammation by inhibiting migration of Langerhans cells [Griffi ths et al, 2001].…”