Polymer device degradation hydrolysis

Based on the above reasons, polymers possessing a variety of degradation rates and mechanisms have been developed however, hydrolysis still remains the predominant degradation mechanism for polymers that are most commonly used in drug delivery applications. Many polymers that are susceptible to hydrolysis, for example, the polyesters PLA and PLG, degrade by random hydrolysis that takes place homogeneously throughout the bulk of the polymer device. In contrast, other classes of polymers, such as the polyanhydrides and polyorthoesters, have been developed in an attempt to yield hydrolysis only at the outer surface of the device that is exposed directly... 

The explanted devices were also examined by scanning electron microscopy and the results shown in Fig. 21 (18). The pictures clearly show a progressive diminution of a central uneroded zone and the development of voids around the periphery of the rod-shaped device. The presence of voids suggest that once erosion starts, generation of hydrophilic degradation products at that location accelerates further polymer hydrolysis. 

Hydrophobic polymers are often used to deliver biomacromolecules regardless of the route of administration. The rapid transit time of approximately 8 hours limits the time of a device in the gastrointestinal (GI) system, consequently the mechanisms possible for oral drug release are limited. The predominant method of release from hydrophobic polymers has been degradation, or biodegradation, of a polymeric matrix by hydrolysis (Figure 11.1). In fact, all of the hydrophobic polymers described in this chapter for use as oral protein or peptide delivery are hydrolytically unstable. 

Poly(ortho esters) offer the advantage of controlling the rate of hydrolysis of acid-labile linkages in the backbone by means of acidic or basic excipients physically incorporated in the matrix. This results in polymer degradation proceeding purely by surface erosion, which results in zero-order drag release from disk-shaped devices. 

Poly(e-caprolactone) (PCL) is synthesized by anionic, cationic or coordination polymerization of e-caprolactone. Degradable block copolymers with polyethylene glycol, diglycolide, substituted caprolactones and /-valerolactone can also be synthesized. Like the lactide polymers, PCL and its copolymers degrade both in vitro and in vivo by bulk hydrolysis, with the degradation rate affected by the size and shape of the device and additives. 

This degradation process is autocatalytic, since the g-hydroxybutyric acid that is produced catalyzes the hydrolysis reaction. To prevent abrupt degradation and erosion, a basic compound must be incorporated into the polymer. For example, sodium bicarbonate can be incorporated into a polymeric device composed of Alzamer to control the rate of polymer degradation and erosion. Although the polymer has been used for a number of drug delivery applications, it is difficult to produce and requires addition of significant amounts of a basic chemical to prevent uncontrolled degradation [21]. 

Because of the instability of the anhydride bond in the presence of water, special properties are required for stable polyanhydride devices. A critical element in the development of polyanhydride biomaterials is controlling hydrolysis within a polymeric device. To obtain implants where hydrolysis is confined to the surface of the polymer, hydrophobic monomers can be polymerized via anhydride linkages to produce a polymer that resists water penetration, yet degrades into low molecular weight oligomers at the poly-mer/water interface. By modulating the relative hydrophobicity of the matrix, which can be achieved by appropriate selection of monomers, the rate of degradation can then be adjusted. For example, copolymers of sebacic acid, a hydrophilic monomer, with carboxyphenoxypropane, a hydrophobic monomer, yield ... 

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