Preparation of chitosan/alginate/calcium complex microparticles loaded with lactoferrin and their efficacy on carrageenan-induced edema in rats.

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.

METHODS

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.

CONCLUSIONS

Chitosan/alginate/calcium complex microparticles are suggested to be useful for promotion of efficacy of LF at oral administration.