Macrophage Activation by Poly(maleic acid-alt-2-cyclohexyl-1,3-dioxap-5-ene) Encapsulated in Polysaccharide-Coated Liposomes

Abstract

An increase in the efficiency of macrophage activation has been tried by en capsulating potent polyanionic polymer immunomodulators into polysac charide-coated liposomes. For this purpose, several alternating copolymers of maleic acid (MA) and itaconic acid (IT) with 2-cyclohexyl-1,3-dioxap-5-ene (CDA), styrene (ST), and other monomers have been synthesized and frac tionated.

First, the interaction between the liposomes and polyanionic polymers was investigated. As a result, poly(maleic acid-alt-2-cyclohexyl-1,3-dioxap-5-ene) (MA-CDA) was found to be the best candidate for encapsulating in the liposome while poly(itaconic acid-alt-styrene)(IA-ST) strongly perturbed these vesicles.

Based on these results, MA-CDA was encapsulated in the mannan derivative- coated liposomes and the macrophage activation activity was evaluated from the superoxide production of the activated macrophages in vivo. Compared with the administration of free MA-CDA, the maximum in the superoxide pro duction appeared faster (2 h after injection) and the activity was significantly increased.

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