7.2. Reductive degradation

to form matrix systems and promoted a significant decrease in the release rate of the model drug theophylline; as a result, it proved to be an excellent controlled release matrix forming excipient. An homopolyurethane with free secondary hydroxyl groups based on 3,4-O-isopropylidene-D-mannitol and 2,2'-dithiodiethyldiisocyanate has been used as sustained matrix forming

Figure 14. Diol monomers synthesized from methyl a-D-glucopyranoside or sucrose and epoxidized methyl oleate.

The reaction of diglycerol dicarbonate, synthesized from diglycerol and dimethyl carbonate, and various diamines led to amorphous poly(hydroxy urethane)s, in bulk at mild temperatures, without any catalyst. The abundance of hydroxyl groups along the polymer backbones allows curing purposes and/or further functionalization [60]. Very rigid polyurethane foams with high cross-linking density were obtained from sorbitol-based polyols. The cross-linking density of the formed PU network was directly modified by the polyol mixture ratio, and microstructure and properties also changed in consonance. The incorporation of different amounts of a diol with longer chain length between hydroxyl groups allowed fixing the

excipient for site-specific drug release in the gastrointestinal tract [59].

rigidity of the foams [61].

180 Aspects of Polyurethanes

Figure 15. Structure of D,L-1,4-dithiothreitol-based polyurethane.

Galbis et al. reported the introduction of disulfide linkage into the polymer backbone of novel reduction-sensitive biodegradable sugar-based polyurethanes. Although hydrolytical degradation of PU has been extensively reported, a faster degradation method under milder degradation conditions was achieved mediated by glutathione (GSH) [21]. Thus, polyaddition reactions of mixtures of 2,2'-dithiodiethanol (DiT) and 2,3,4-tri-O-methyl-L-arabinitol (25), 2,3,4-tri-O-benzyl-L-arabinitol (29) or L-arabinitol (35) to HDI (3) were carried out (Figure 18). PU(DiT-HDI) homopolymer exhibited high crystallinity but the introduction of the L-arabinitol-based diols led to a reduction in the crystallinity of the copolymers. All the copolyurethanes were biodegraded under physiological conditions being crystallinity an important factor in the degradation rate. Thus, the amorphous copolymers with low DiT repeating unit contents were more easily cleaved, despite the lower disulfide ratio. Their DiT repeating units do not pack into semicrystalline segments and

Figure 16. Linear polyurethanes derived from O-protected alditols.

were, as a result, more accessible to the reducing agent. Therefore, the amorphous copolymers PU [(ArBn80-DiT20)-HMDI] and PU[(ArMe80-DiT20)-HMDI] were those with enhanced degradation trends.

Figure 17. Copolyurethanes derived from 1,4-di-S-benzyl-D,L-dithiothreitol.

Figure 18. Copolyurethanes degradable by glutathione under physiological conditions.
