Substituted poly(methyl vinyl ether-alt-maleic anhydride) for the release control and targeting of methotrexate

Poly(methyl vinyl ether-alt-maleic anhydride) substituted with cholamine (CA), aminoethylcholamine (AECA), or aminooctyl-cholamine (AOCA) at different substitution degrees, were used for methotrexate (MTX) complexation. The solid complexes, isolated by precipitation from the preparative mixture, showed lower fractional releases at pH 7.4 than at 5.5. This was ascribed to the establishment of ionic interactions between the ionized carboxyls of both the polymer and the drug and the quaternary ammonium groups of the substituents (CA, AECA, AOCA) inducing polymer self-aggregation and thus complex stabilization. The fractional release in pH 7.4 decreases with the increase in the substitution degree until a minimum characteristic for each substituent analyzed is reached and then rises with the increase in substitution degree. The minimum release at pH 7.4 was observed in the presence of AECA at the degree of substitution corresponding to 0.35 mole of substituent per mole of dimer (methyl vinyl ethermaleic anhydride). None of the substituted polymers studied had any haemolytic effect, indicating good biocompatibility.