Biodegradable polyanhydride polymers

This chapter explores the development of biodegradable polyanhydride polymers as a local chemotherapeutic delivery system in brain tumor patients. In so doing, the authors detail the unique pharmacokinetic considerations inherent in CNS drug delivery, and the resultant advantages of local administration. Subsequent sections chronicle the development of biocompatible technologies, preclinical and clinical experience with polymer-based tumor treatments, and potential future advancements in local antineoplastic drug delivery. 

Polyanhydrides, such as poly[bis(p-carboxyphenoxy)propane sebacic acid] copolymers (Figure 4.14), are also used for the fabrication of biodegradable implants. Polymer degradation occurs via hydrolysis, the biscarboxyphenoxypropane monomer is excreted in the urine and the sebacic acid monomer is metabolized by the liver and is expired as carbon dioxide via the lung (Figure 4.14). 

Domb, A.J. Ehrenfreund, T. Golenser, J. Langer, R. Israel, Z. Biodegradable polyanhydrides synthesis and drug delivery applications. Biodegrad. Polym. 2003,2, 121-151. 

Hydrolysis is the most common mechanism of polymer degradation in biomaterials. Of the linkages that commonly occur in polymers, the anhydride linkage is one of the least stable in the presence of water. In fact, polyanhydride polymers are so sensitive to water that they are unsuitable for many potential applications. However, the potential for rapid hydrolysis of the polymer backbone makes anhydride-based polymers attractive candidates as biodegradable materials. 

The use of lipids, including lipid-protein membranes, concentric lipid manbranes, and submicron ultrathin lipid membranes is another common approach. Biodegradable synthetic polymers offer another approach. The first one used was polylactide. Many types of polylactides and poly-glycolic acids are now used for artificial cells. Other synthetic biodegradable polymers, such as polyanhydride, also are used. The use of biodegradable artificial cells has become an active field. 

D. Hepatocyte transplantation Our initial polymer design was that of a small wafer of biodegradable polyanhydride. Hepatocytes were seeded in a monolayer onto the wafer in culture and then placed into the recipient animal while on the disc. We found that the cell number and cell density were inadequate for reliable successful engraftment when using this polymer design. Our preliminary studies indicated that for adequate hepatic function, we would need to implant at least 10% of the number of cells found in a normal liver(28). We... 

The overall science around polyanhydrides is summarised in Figure 5.1. The main focus of this chapter is to introduce and provide an extensive review of the various promising aspects of one specific class of synthetic biodegradable medical polymer — poly anhydride. In the first part of the chapter the classification, chemical stmctures, and synthesis methods of various polyanhydrides are discussed. This is followed by a discussion of the in vitro and in vivo behaviour and degradation mechanism of these materials. Also, the various processing techniques that are employed are introduced and explained. Finally, medical applications of polyanhydride systems are presented, highlighting their role and their potential to be used as a family of medical polymers of the future generation . 

Mader, K., Nitschke, S., Stosser, R., Hans-Hubert, and Domb, A.J. (1996d) Nondestractive and localized assessment of acidic microenrironments inside biodegradable polyanhydrides by spectral spatial Electron Paramagnetic Resonance Imaging. Polymer, in press. 

Dang, W. and Saltzman, W.M., Controlled release of macromolecules from a biodegradable polyanhydride matrix. J. Biomater. Sci., Polym. Ed., 1994,6 291-311. 

A biodegradable polyanhydride has been prepared by polycondensation of a lithocholic acid dimer (Scheme 11b). The homopolymer has a Tg of 85°C and a melting point of >250°C, both of which can be lowered by the incorporation of a comonomer (sebacic acid). The polymers have been subjected to degradation and release studies, using p-nitroanUine as the model drug. The degradation and release rates are found to be dependent on the copolymer composition, and no apparent toxicity is observed in vivo [110]. 

Two other series of biodegradable polymers that depend upon chain degradation are the polyanhydrides and the polyorthoesters. Both of these polymers contain hydrophobic units linked together along the polymer chain by functional... 

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