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Among anionic polymers considered as topical microbicides to prevent sexual transmission of HIV-1 {Carbomer 974P/BufferGel, carrageenan, CAP, cellulose sulfate, dextran/dextrin sulfate, poly(napthalene sulfonate) and poly(styrene-4-sulfonate)}, CAP formulated in a micronized form, is the only compound which has a capacity to remove from physiological fluids infectious virus by adsorption onto the micronized particles.
They include: (1) sulfate esters of polysaccharides {carrageenan [ 1 16 17 18 19 ] , cellulose sulfate [ 12 13 14 15 ] , and dextran or dextrin sulfate [ 1 2 3 4 5 6 7 8 9 10 11 ] }; (2) aryl sulfonates {poly(naphthalene sulfonate) [ 22 23 24 ] and poly(styrene-4-sulfonate) [ 20 21 ] }; and (3) aliphatic {Carbomer 974P/BufferGel [ 25 26 27 28 29 ] } and aromatic carboxylates {CAP [ 30 31 32 33 34 35 36 37 ] }. The anti-HIV-1 properties of these polymers are expected to depend on their complexation with virus proteins which is likely to occur mainly through the formation of salt linkages or ion pairs between oppositely charged groups on the polymers and virus proteins, respectively [ 56 ] . However, the anti-HIV-1 properties of these polymers may depend not only on their charge density, but also on the characteristics of their uncharged portions, which may be involved in hydrophobic and hydrogen bonding interactions which can elicit profound conformational changes in hydrophobic regions of proteins and cause disassembly of complex proteins consisting of subunits [ 57 ] . For these reasons it is not be expected that all anionic polymers, considered as anti-HIV-1 microbicides, would have similar biological activities.
In repeated experiments with HIV-1 IIIB, soluble and micronized CAP, cellulose sulfate, poly(naphthalene sulfonate), poly(styrene-4-sulfonate) and BufferGel, respectively, caused a ≥ 140-fold reduction in infectivity, while dextran sulfate, carrageenan and Carbomer 974P (pH 7), respectively, were less effective (4- to 25-fold reduction in infectivity).
Among the sulfonates and polysaccharide sulfates, carrageenan and poly(napthalene sulfonate) had lower anti-coagulant activity in comparison with cellulose sulfate, dextran sulfate and poly(styrene-4-sulfonate) (Fig.
This might be due to the polysaccharide backbone of cellulose [ 60 ] with a propensity to form strong intermolecular hydrogen bonds and to be involved in hydrophobic interactions more than soluble dextrans [ 61 ] and galactose + 3,6-anhydrogalactose copolymers (= the saccharide moiety of carrageenan) [ 62 63 ] . Among the two polymers containing aryl sulfonates, poly(napthalene sulfonate) was more effective than poly(styrene-4-sulfonate) with respect to induction of gp41 six-helix bundles in HIV-1 BaL.
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