In situ activation of murine peritoneal macrophages by cyclohexyl-1,3-dioxepin and 4-methyl-2-pentenoyl maleic anhydride copolymers.

Peritoneal macrophages (PM theta) from mice treated intraperitoneally with the unique polyanionic compounds cyclohexyl-1,3-dioxepin maleic anhydride copolymer (CDA-MA) and 4-methyl-2-pentenoyl maleic anhydride copolymer (MP-MA) had tumoricidal activity against Lewis lung tumor cells. 5'-Nucleotidase ectoenzyme activity, which had previously been associated only with nontumoricidal, resident PM theta, was elevated in tumoricidal PM theta elicited with CDA-MA and MP-MA. Cell counts and differentials performed on peripheral blood leukocytes and PM theta populations from CDA-MA- and MP-MA--treated mice more closely corresponded to those of normal mice than mice treated with the conventional PM theta-activating agents pyran and Corynebacterium parvum. In addition, the lysosomal peroxidase activity in PM theta after administration of CDA-MA and MP-MA remained at levels comparable with normal resident PM theta, while an influx of peroxidase-positive macrophages was observed after administration of pyran and C. parvum. Inoculation of CDA-MA and MP-MA into mice bearing Lewis lung carcinoma showed a significant increase in median survival time compared with control mice, as well as an increase in the percentage of mice that survived greater than 90 days. Taken together, these data suggest that CDA-MA and MP-MA activated PM theta in situ and prolonged survival against primary transplanted Lewis lung carcinoma.

Biological activity of maleic anhydride copolymers. I. Biocompatibility and antitumoural effects of maleic anhydride-vinyl acetate, maleic anhydride-methyl methacrylate and maleic anhydride-styrene copolymers.

A series of maleic anhydride (MA)-vinyl acetate (VA), MA-methyl methacrylate (MM), and MA-styrene (S) copolymers were prepared and characterized. On employing various amounts of initiator, maleic anhydride-vinyl acetate, methyl methacrylate, and styrene copolymers with molecular weights ranging between 18,000 and 200,000 have been obtained. The in vivo and in vitro tests performed on K562 cellular cultures (human chronic myeloid leukemia) have shown that, as a function of the molecular weight, the synthesized copolymers demonstrate a 50% in vitro cytotoxicity and an average tumour regression of maximum 68%.

Drug delivery systems based on inorganic materials: I. Synthesis and characterization of a zeolite-cyclophosphamide system.

Porous material of the CuX zeolite type has been synthesized and used as support for a classic antitumoral drug--cyclophosphamide (CP). The new material obtained represents a physical mixture of the two components. In vivo tests allowed biochemical and anatomopathological evaluation of antitumoral effects determined by oral administration of the CuX zeolite-CP system. Data obtained show that the intensity of the antitumoral effects of the CuX zeolite-CP system is similar as compared to that achieved by CP. A possible advantage of the CuX zeolite-CP system is the continual maintenance in the blood of a CP concentration ranging between 100 and 1,000 ng ml-1 plasma.