Liposomalization of Lactoferrin Enhanced It's Anti-inflammatory Effects via Oral Administration

Abstract

It is known that lactoferrin is one of the functional proteins contained in mammalian milk and that it plays an important role in the immune system. In this study, we prepared multi-lamellar liposomal bovine lactoferrin composed of egg yolk phosphatidylcholine and phytosterol for oral delivery, and examined any resulting anti-inflammatory effects. Oral pretreatment of liposomal lactoferrin exhibited more suppressive effects than did nonliposomal lactoferrin on CCl 4 -induced hepatic injury in rats as well as on lipopolysaccharide-induced TNF-alpha production from mouse peripheral blood mononuclear leukocytes. Further investigation revealed that the liposomalization did not exert influence on the absorbability of lactoferrin to the venous blood or lymph following an intraduodenal administration in rats. Furthermore, there was no significant difference exhibited between the antigenicity of liposomal and non-liposomal lactoferrin, which was measured using the passive cutaneous anaphylaxis reaction following oral sensitization to them in guinea pigs. These results suggest that liposomal lactoferrin might act more effectively than conventional lactoferrin in the intestinal site, which is regarded as an active site of orally administered lactoferrin, although the biological mechanism is not fully understood yet. Consequently we propose that liposomal lactoferrin could be a novel active constituent useful for preventive and therapeutic treatment of inflammatory diseases.

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.…”

“…In fact, LPS-induced TNF-a production by the peripheral monocytes of the mice with orally administrated bLF for 7 days was remarkably reduced. 22 Recently, it is reported that LPS-induced TNF-a production was suppressed by bLF through its inhibition of binding of NF-kB to the TNF-a promoter after internalization of bLF in monocytic cell. 15 It is reasonable to consider that internalized bLF may also reduce LPS-induced TNF-a and RANKL production by inhibiting the binding of NF-kB to TNF-a promoter in OBs.…”

“…22 LPS from Aggregatibactor Actinomycetemcomitance (ATCC29522 strain) (A.a.-LPS) was kindly provided by Professor Tatsuji Nishihara of the Kyusyu Dental College.…”

“…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.…”

Lactoferrin as an Adjunctive Agent in the Treatment of Bacterial Infections Associated with Diabetic Foot Ulcers

“…Some pharmaceutical formulations of lactoferrin, including liposomes administered intraarticularly in joints (Trif et al, 2001) or by oral route (Ishikado et al, 2005) to control the chronic inflammation of arthritis or other pathologies, as well as bioadhesive tablets administered to treat inflammation associated with oral ulcers Takeda et al, 2007), may represent systemic or oral delivery formulations for adjunctive treatment of chronic wounds. As is known, a prolonged inflammatory response is a contributing factor of chronic wounds, since it abrogates the normal process of ulcer healing (Pierce, 2001).…”