New macromolecular micelles based on degradable amphiphilic block copolymers of malic acid and malic acid ester

To study the behaviour of polymeric materials under in-vivo conditions, deg radable macromolecular micelles based on amphiphilic block copolymers of po ly(beta-malic acid) as hydrophilic units and poly(beta-malic acid alkyl est ers) as hydrophobic blocks are studied. First three beta-substituted beta-l actones, benzyl malolactonate, butyl malolactonate, and butyl 3-methylmalol actonate were prepared, starting from aspartic acid. A prepolymer based on benzyl malate units was synthesized by anionic ring-opening polymerization of benzyl malolactonate. Then the carboxylic end groups of this prepolymer were used as initiator for the polymerization of the second lactone, e.g. b utyl malolactonate or butyl 3-methylmalolactonate. The prepolymer and block copolymers have been characterized by H-1 NMR and size exclusion chromatog raphy (SEC). Degradable macromolecular micelles were prepared from the bloc k copolymers by two different methods and characterized by dynamic light sc attering and fluorescence measurements using pyrene as a fluorescence probe . It was shown that these amphiphilic degradable copolymers from stable mic elles under physiological conditions (10(-2) M phosphate buffered solution, PBS, pH 7.4 with 0.15 M NaCl). Moreover, it was displayed that the charact eristics of these macromolecules micelles, especially the critical micellar concentration (cmc), are depending on the chain length of both blocks and on the chemical structure of the hydrophobic block. A very important conclu sion of this study is, that micelle formation is dependent on the pH of the medium. Therefore, besides that fact that such micelles are potentially de gradable into non-toxic low molecular weight molecules, their properties an d stability were proven to be pH-dependent. This property can lead developm ent of an "intelligent" drug carrier able to release the entrapped biologic ally active molecule depending on the pH values.