BACKGROUND: Although lactoferrin (LF) possesses useful functions such as antitumor, antiviral, and anti-inflammatory acitivities, it is subject to gastric digestion, resulting in the reduction of efficacy. Therefore, it is important to develop a system delivering LF efficiently to intestinal mucosa or gut-associated lymphoid tissue. METHOD: Chitosan/alginate/calcium complex microparticles containing LF at a high loading were prepared using alginate, LF, and calcium chloride at the ratio of 6:3:8 (w/w). The release test was performed using Japanese Pharmacopoeia, Fifteenth Edition (JP15) first fluid (pH 1.2) for initial 2 hours, followed by JP15 second fluid (pH 6.8) for another 5 hours. Furthermore, the in vivo efficacy was evaluated from anti-inflammatory effect using rats with carrageenan-induced edema, in which dosing was performed intragastrically at 50 mg LF eq./kg 5, 3, and 1 days before carrageenan injection. RESULTS: Microparticles have 20-30 % (w/w) LF content and 1-3 mm size. Nearly 60 % of LF was released at pH 1.2 at the first 1 hour, and then slowly released up to 80% at 7 hours. Suppressive effect against the edema was greater in the order of microparticles LF solution control (saline). Initial burst of LF from microparticles was not associated with their promoted efficacy. CONCLUSION: Chitosan/alginate/calcium complex microparticles are suggested to be useful for promotion of efficacy of LF at oral administration.
BACKGROUND: Although lactoferrin (LF) possesses useful functions such as antitumor, antiviral, and anti-inflammatory acitivities, it is subject to gastric digestion, resulting in the reduction of efficacy. Therefore, it is important to develop a system delivering LF efficiently to intestinal mucosa or gut-associated lymphoid tissue. METHOD:Chitosan/alginate/calcium complex microparticles containing LF at a high loading were prepared using alginate, LF, and calcium chloride at the ratio of 6:3:8 (w/w). The release test was performed using Japanese Pharmacopoeia, Fifteenth Edition (JP15) first fluid (pH 1.2) for initial 2 hours, followed by JP15 second fluid (pH 6.8) for another 5 hours. Furthermore, the in vivo efficacy was evaluated from anti-inflammatory effect using rats with carrageenan-induced edema, in which dosing was performed intragastrically at 50 mg LF eq./kg 5, 3, and 1 days before carrageenan injection. RESULTS: Microparticles have 20-30 % (w/w) LF content and 1-3 mm size. Nearly 60 % of LF was released at pH 1.2 at the first 1 hour, and then slowly released up to 80% at 7 hours. Suppressive effect against the edema was greater in the order of microparticles LF solution control (saline). Initial burst of LF from microparticles was not associated with their promoted efficacy. CONCLUSION:Chitosan/alginate/calcium complex microparticles are suggested to be useful for promotion of efficacy of LF at oral administration.