Bioerodable degradation

Poly(orthoesters) represent the first class of bioerodible polymers designed specifically for dmg deUvery appHcations (52). In vivo degradation of the polyorthoester shown, known as the Al amer degradation, yields 1,4-cydohexanedimethanol and 4-hydroxybutyric acid as hydrolysis products (53). 

Hie ester linkage of aliphatic and aliphatic-aromatic copolyesters can easily be cleaved by hydrolysis under alkaline, acid, or enzymatic catalysis. This feature makes polyesters very attractive for two related, but quite different, applications (i) bioresorbable, bioabsorbable, or bioerodible polymers and (ii) environmentally degradable and recyclable polymers. 

Deong, K. W., Brott, B. C., and Danger, R., Bioerodible polyanhydrides as drug-carrier matrices. I. Characterization, degradation and release characteristics, J. Biomed. Mater. Res., 19, 941-955, 1985. 

It is important to distinguish between erosion and degradation. Erosion is mass loss from a bioerodible polymer and may be a consequence of polymer dissolution or degradation of the polymer backbone, followed by dissolution of the degradation products. Degradation typically occurs by hydrolysis of the polymer backbone, the kinetics of which is a function of the polymer chemistry. Thus, erosion is the sum of several elementary processes, one of which may be polymer degradation. 

Modeling the behavior of bioerodible polyanhydrides is complicated by the many phenomena contributing to release profiles described in the previous section. The degradation kinetics may be coupled to other processes, such as diffusion and dissolution, and the overall erosion kinetics represent the sum of all of these multiple processes (Goepferich, 1996a). 

Varshney et al. (3) prepared biocompatible and bioerodable poly(lactide-co-succinic anhydride) derivatives having a Young s modulus between about 1.5 and 3, which had enhanced surface degradation rates. 

Toxic degradation products this effect is applicable to biodegradable polymers for example, degradation of poly(alkylcyanoacrylate) leads to the formation of formaldehyde which is considered toxic in humans. In the case of a bioerodible polyvinylpyrrolidone), the accumulation of the dissolved polymer in the liver raises a longterm toxicity issue. 

In bioerodible drug delivery systems various physicochemical processes take place upon contact of the device with the release medium. Apart from the classical physical mass transport phenomena (water imbibition into the system, drug dissolution, diffusion of the drug, creation of water-filled pores) chemical reactions (polymer degradation, breakdown of the polymeric structure once the system becomes unstable upon erosion) occur during drug release. 

Polyanhydrides are a class of bioerodible polymers that have shown excellent characteristics as drug delivery carriers. The properties of these biomaterials can be tailored to obtain desirable controlled release characteristics. Extensive research in this promising area of biomaterials is the focus of this entry. In the first part of the entry, the chemical structures and synthesis methods of various polyanhydrides are discussed. This is followed by a discussion of the physical, chemical, and thermal properties of polyanhydrides and their effect on the degradation mechanism of these materials. Finally, a description of drug release applications from polyanhydride systems is presented, highlighting their potential in biomedical applications. 

Experiments were also performed to evaluate whether the extent of enhancement could be regulated externally. By varying the ultrasound intensity, the degree of enhancement for both polymer degradation and drug release for the bioerodible and non-erodible systems could be altered 10-fold (42). 

MAJOR APPLICATIONS Polymers have shown promise as bioerodible materials capable of (controlled degradation and sustained drug delivery for therapeutic cmd other related uses/ Polyphosphazenes have been evaluated for approximately two decades, but resecirch has become more focused in recent years. 

In vitro evaluations have been made. Bioerodible poly(phosphazenes) have the advantage that the degradation products are biocompatible. The majority of bioerodible poly(phosphazenes) have been synthesized by the classical thermal procedure of Allcock et al. (1965)—reference (15). The copolymer in question is described. In vivo performances in clinically relevant conditions are planned for PPHOS matrices. 

Most bioinert rigid polymers are commodity plastics developed for nonmedical applications. Due to their chemical stability and nontoxic nature, many commodity plastics have bwn used for implantable materials. This subsection on rigid polymers is separated into bioinert and bioerodable materials. Table 11.6 contains mechanical property data for bioineit polymers and is roughly ordered by elastic modulus. Polymers such as the nylons and poly(ethylene terephthalate) slowly degrade by hydrolysis of the polymer backbone. However, they are considered bioinert since a significant decrease in properties takes years. 

Most rigid degradable polymers degrade without the aid of enzymes and are therefore bioerodable. Table 11.7 shows mechanical property data for bioerodable polymers. 

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