Abstract: A drug delivery system for delivering a drug payload to a specific tissue or cell type is disclosed. The system includes a polymalic acid molecular scaffold which can be used for attaching a plurality of molecular modules. Molecular modules include targeting antibodies for promoting cellular uptake by a target cell, and pro-drugs for altering cellular metabolism, for example, a pro-drug that alters expression of protein kinase CK2.

Abstract: A drug delivery system for delivering a drug payload to a specific tissue or cell type is disclosed. The system includes a polymalic acid molecular scaffold which can be used for attaching a plurality of molecular modules. Molecular modules include targeting antibodies for promoting cellular uptake by a target cell, and pro-drugs for altering cellular metabolism, for example, a pro-drug that alters expression of protein kinase CK2.

Abstract: A structured drug system that is useful for delivering a drug payload to a specific tissue or cell type is disclosed. The system is based on purified polymalic acid. This polymer isolated from natural sources is biocompatible, biodegradable and of very low toxicity. The polymer is extremely water soluble and contains a large number of free carboxyl groups which can used to attach a number of different active molecules. In the examples disclosed N-hydroxysuccinimide esters of the carboxyl groups are used to attach such molecules. The active molecules include monoclonal antibodies to promote specific cellular uptake and specific pro-drugs such as antisense nucleic acids designed to modify the cellular metabolism of a target cell. The pro-drugs are advantageously linked by a somewhat labile bond so that they will be released under specific conditions. In addition, the system contains amide-linked valine to encourage membrane disruption under lysosomal conditions.

Abstract: The invention is a large-scale production and purification of beta-poly(L-malic acid), biodegradable natural polyester of L-malic acid of molecular weight 30,000 to 300,000 from plasmodia of the Physarum family, especially Physarum polycephalum. This will replace previous laborious and uncontrolled production by bioreactor methods of high productivity and quality, especially to obtain pure polymer of high molecular weight. The described 20-liter bioreactor method can be scaled up for industrial purpose at optimal production and minimum growth time to prevent degradation The invention includes the method of isolation of polymalic acid of 100,000 Mn (number-averaged molecular weight) from the culture broth optimized towards high yields of extremely pure polymalic acid. The non-hygroscopic, water and organic solvent-soluble polymer is endotoxin and agglutinin free and ready to use in chemical syntheses.