Interesting Properties of Polymalic Acid and its Application in Drug Delivery

Eggehard Holler and Bong-Seop Lee

Institut fuer Biophysik und Physikalische Biochemie, Universitaet Regensburg, D-93040 Regensburg, Germany

Polymalic acid is a linear polyester of L-malic acid involving the hydroxyl and 3-carboxyl groups of the hydroxy dicarbonic acid. It is a typical constituent of the plasmodial cell type of Physarum polycephalum. Polymalate binds specifically to nucleic acid interacting proteins via its abundant carboxylates and is supposed to aid their equal distribution over the giant plasmodium as a molecular carrier and storage device. The further function in the plasmodium is organized by an adapter protein that binds to the OH-terminus of the polymer and that cleaves it hydrolytically after exocytosis. Polymalic acid is biodegradable, nontoxic, and nonimmunogenic. After chromatographic purification from the culture broth, the polymer is available as acid or in various salt forms. The pending carboxylates can be used in controlled drug delivery as a scaffold to ligate products, drug releasing modules, endosome disrupting modules, and cell targeting modules. Chemical coupling of the various biologically functional modules is followed by routine preparative techniques.

Lee, B.-S., Vert, M., and Holler, E. (2002) Water-soluble aliphatic polyesters: Poly(malic acid)s. Biopolymers (Doi, Y. & Steinbuechel, A., eds) pp. 75-103, Wiley-VCH, New York