OPTIMIZATION OF POLY(MALEIC ACID-ALT-ACYCLOHEXYL-1,3-DIOXEPIN-5-ENE) FOR ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITY

A polymeric drug, poly(maleic acid-alt-2-cyclohexyl-1,3-dioxepindene) [poly(MA-CDA)], with molecular weights of 2,500 and 5,400 exhibited antiviral activity against HIV in vitro. These molecular weights were found to be too low for effective in vivo activity. To enhance the antiviral effect in vivo, the free radical copolymerization of maleic anhydride and 2-cyclohexyl-1,3-dioxepin-5-ene was optimized. The highest molecular weight was obtained by direct synthesis was 22,000 after solution fractionation. Poly(MA-CDA)'s with higher molecular weights were synthesized by polymer-polymer grafting. The original poly(MA-CDA) was modified with ethanolamine to form p-hydroxy amides along the polymer chain. The modified poly(MACDA) was then reacted with the original poly(MA-CDA) by means of their anhydride groups. The molecular weight of grafted products was controlled by varying the molar ratios of the modified polymer to the original polymer.