Poly(glutamic acid): From natto to drug delivery systems

Poly(glutamate)s exist as the naturally occurring poly(γ-glutamic acid) and the synthetically prepared poly(α-glutamic acid). Salts and esters of poly(glutamic acid) are referred to as poly(glutamate)s. The preparation and use of synthetic and naturally occurring poly(glutamate)s are reviewed in this article. Both polymeric isomers carry a terminal carboxyl group in their side chains, which gives poly(glutamic acid) its physical properties, such as hydrophilicity, capabilities for electrostatic interactions, hydrogel formation and makes the polymer suitable for polymer analogous reactions. Poly(γ-glutamic acid) is produced by microbial fermentation of various Bacillus species. Typically, soybeans are fermented by B. subtilis to give natto, the most widely known form of poly(γ-glutamic acid). Agricultural surplus, such as rice straw, molasses, and corn stalks, have been investigated as carbon sources for the bacterial fermentation. While the yields are above or comparable to those of soybean fermentation, 25–40 g/L, the preparation of the feed stocks must be considered in cost analyses. Aside from the food sector, poly(γ-glutamic acid) is used in cosmetics for its water holding capacity, and hydrogels are considered for biomedical applications. Poly(α-glutamic acid) is prepared by the ring-opening polymerization, ROP, of glutamic acid N-carboxyanhydride for applications almost exclusively in the biomedical sector. The strict control over the molecular weight guaranteed by ROP yields polymers with a low (∼1.1) polydispersity as required in drug delivery applications and the reactive carboxyl side groups allow for covalent attachment of drugs and imaging reagents, thus allowing for theranostics applications. The anionic character of the polymer is exploited in layer-by-layer constructs with cationic polymers, such as chitosan, to build drug delivery vehicles.