Styrene maleic acid copolymer-conjugated

A very original application is the use of insoluble, polymeric Gd(III)-chelates as coating materials e.g., on the polypropylene catheters used for medical purposes (97). To poly(styrene-maleic acid) copolymer (SMA), HEDTA was conjugated and the Gd(III) ions were complexed by the resulting polymer, forming SMA-HEDTA-Gd(III). As a variation, the citric acid-HEDTA-SMA polymer was synthesized and used for chelating the Gd(III)ions, forming SMA-HEDTA-citric acid-Gd(III). The Gd(III) contents were 3.75 and... 

Oda T, Maeda H. Binding to and internalization by cultured cells of neocarzinostatin and enhancement of its actions by conjugation with hpophihc styrene-maleic acid copolymer. Cancer Res 1987 47 3206 3211. 

Examples of clinically validated water-insoluble, biodegradable polymers include material such as poly(D,L,lactide-c< -glycolide (PLGA) poly(ortho esters) (POE) and polyisohexylcyanoacrylate (PIHCA) These materials have been used for the preparation of nanoparticles, biodegradable implants and viscous injectable materials. In addition, one amphiphilic material, poly(styrene-co-maleic acid) copolymer conjugated with neocarzinostatin (SMANCS) dissolved in lipid contrast medium Lipiodol, has proven efficacious in several clinical tri s for the treatment of cancer... 

Glucoamylase (conjugated with ethylene-maleic acid or styrene-maleic acid copolymers) D-Glucose isomerase... 

Initially, Maeda et al. conjugated an antitumor protein neocarzinostatin (NCS, MW 12 kDa) with copolymer of styrene-maleic acid half-w-butylate (SMA) [59-61]. The eonjugation of protein (NCS) with SMA called SMANCS... 

Modification of hydrophilic proteins with hydrophobic polymers has been also explored as a way to enhance protein transport into a cell. For example, conjugation of a small water-soluble peptide neocarzinostatin, with poly(styrene-co-maleic acid) copolymer (SMANCS) resulted in a 20 to 30 fold enhancement ofthe transport ofthe peptide into a cell. This polymer conjugate also displayed facilitated uptake into cells at acidic pH, which may be due to protonation of carboxylic groups of the polymer chain rendering it even more hydrophobic. Since more acidic environment is... 

An active, water-soluble, immobilized form of glucoamylase was obtained when the enzyme reacted with derivatives of testosterone. Highly-charged, water-soluble conjugates of glucoamylase and a copolymer of either ethylene and maleic acid or styrene and maleic acid are absorbed onto particles of DEAE-cellulose to give immobilized derivatives of the enzyme. ... 

One can of course ask why only PEG is chosen for protein modification instead of other polymers. Actually, very few examples of conjugation with other polymers have been reported so far, the most successful being the poly(styrene-co-maleic acid/anhydride) derivative of neocardnostatin (SMANCS) developed by Maeda [118]. The main reason Hes in the mono-functionahty of mPEG that avoids a cross-linking reaction with the polyfunc-tionalized proteins. The usual natural or synthetic polymers present multiple points of attachment in the same molecule. This is the case of polysaccharide, for instance, but also for the extensively studied poly(N-(2-hydroxypropyl) methacrylamide) copolymers (HPMA) [119]. 

Monomers with electron-rich double bonds produce one-to-one copolymers with monomers having electron-poor double bonds in reaction systems that also contain certain Lewis acids. These latter are halides or alkyl halides of nontransition metal elements, including AlCb, ZnCh, SnCL, BF3, AI(CH2CH3)Cl2, alkyl boron halides, and other compounds. The acceptor monomer generally has a cyano or carbonyl group conjugated to a vinyl double bond. Examples are acrylic and methacrylic acids and their esters, acrylonitrile, vinyl ketones, maleic anydride, fumaric esters, vinylidene cyanide, sulfur dioxide, and carbon monoxide. The variety of donor molecules is large and includes various olefins, styrene, isoprene, vinyl halides and esters, vinylidene halides, and allyl monomers [30]. 

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