The biologic activity of polyanions: Past history and new prospectives

Abstract

SYNOPSISThe toxicology of synthetic polyanions relates to molecular weight. This developed from experience with pyran copolymer (divinyl ether maleic anhydride copolymer), which was tested clinically as an antitumor agent and found to be too toxic for continued clinical trial. Synthetic polyanions of low molecular weight are potent stimuli to macrophage phagocytic function and possess antitumor activity. Increased host resistance to pathogens including bacteria, fungi, viruses, and trypanosomes is seen. In contrast to lower-molecular-weight fractions, higher-molecular-weight samples inhibit macrophage function, and apparently increased molecular weight > 15,000 is necessary for antiviral and immunologic stimulating capacity. One possible mechanism for the action of polyanions may relate to redistribution of calcium ions within the cell and increasing cyclic GMP activity. This is a redefinition for the role of polyanions in sol -gel alteration in cytoplasm. The killing effect of the polyanion-activated macrophage on tumor cells resembles that of the polyanion on the nucleus. Polyanions may be potent controllers of the stability of DNA within the nucleus and can act to derepress cells to turn on protein synthesis or, alternatively, inhibit enzymes involved in virus synthesis and control of RNA or DNA polymerase. Thus, they are cogent tools in an understanding of the physiology of nuclear interaction. Biological use for these agents can be developed not only in clinical approaches to inhibition of tumor or viral infection, but to eliminate plutonium, and provide selective enzyme inhibition and protein interaction which allows for isolation, neutralization, and characterization of blood and tissue protein and glycoprotein fractions vital for a wide range of pathophysiology.(1,000,ooO M.W.) Sulf. Chitoran Sulf. Pectic Acid AmidsSulf. Oxid. Cellulose Hydroxornic Acid Laminorin Sulfate aAll animals showed 10% body weight loss. Legend: +, % inhibition 50% or greater; (+), 30-49%. b leukemia [48, 59-621, C3H mammary tumor transplants [62], methylcholanthrene derived transplants [63], and dimethylbenzanthracene (DMBA) induced tumors [64], the LSTRA sarcoma [58], Madison lung carcinoma [65] and prostatic adenocarcinoma in the rat [66], and the M109 lung carcinoma and colon tumor [67]. Pyran prevents polyoma induced tumors and Rauscher leukemia in thymectomized mice [57]. Pyran induces interferon in both humans and mice [16 -18, 52, 681, but antitumor and antiviral activity do not correlate with interferon induction [25, 54, 691. Pyran can both stimulate and inhibit host immune response [l, 2, 25, 70 -761 and alter in vitro lymphoblastic response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) [70 -741. Pyran inhibits the early cation-dependent steps of complement activity (G. S. White, personal communication, 1976) [77, 781, but can activate the C3 bypass. Pyran can prevent adjuvant induced arthritis [76], and its effects on skin graft survival are controversial. Toxicologically, the clinically tested pyran fraction...

Hybrid DIVEMA/PLGA nanoparticles as the potential drug delivery system

“…An attractive candidate for this approach is the copolymer of divinyl ether with maleic anhydride widely known as DIVEMA. This remarkable polymer extensively studied in the 70s and 80s exhibits the broad spectrum of biological activities such as induction of biological response to tumors, antiviral and antibacterial activity explained most probably by induction of interferon production and/or macrophage activation [11,12]. Due to this per se activity, DIVEMA became one of the rst synthetic polymers clinically tested as the anticancer agent; however, despite the antitumor activity evidenced in numerous preclinical studies, no signi cant effect was observed in humans [13,14].…”

A novel vaccine adjuvant based on straight polyacrylate potentiates vaccine-induced humoral and cellular immunity in cynomolgus macaques

“…Polyelectrolytes are widely known for their immunostimulatory properties. [5][6][7] We recently introduced a novel adjuvant, termed SPA09, based on high molecular weight linear polyacrylate readily available and easy to formulate with vaccine antigens. 8 In previous studies in mice, SPA09 was found to work as a strong T H 1-type adjuvant when tested with various types of antigens including the recombinant glycoprotein CMV-gB and a Staphylococcus aureus polysaccharide conjugate (patent WO2017218819A1).…”

“…Polyelectrolytes are widely known for their immunostimulatory properties. 5–7 We recently introduced a novel polyelectrolyte adjuvant, termed SPA09, based on high molecular weight linear polyacrylate (PAA) readily available and easy to formulate with vaccine antigens. 8 …”

A potent novel vaccine adjuvant based on straight polyacrylate

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