Protein/hydrophobic polymer matrix system

Figure 9.10 Proteins are released from matrices by diffusion through constricted pores. Schematie view of a protein/hydrophobic polymer matrix system, (a) Cross-sectional views of matrices at two different loadings. At higher loadings connected clusters of pores are formed, providing continuous paths for diffusion to the surface.

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. 

One particular hydrophobic polymer, EVAc, has been investigated extensively as a matrix system for protein delivery. This polymer is biocompatible, a major consideration because of the interest in developing systems for human health. Other classes of hydrophobic polymers, like silicone elastomers and polyurethanes, may also be useful for controlled protein delivery, although there are fewer examples available in the literature. Nondegradable, hydrophilic polymers, such as poly(2-hydroxyethyl methacrylate) [p(HEMA)], are also biocompatible but usually release proteins over a relatively short period. However, a few examples oflong-term release of peptides and proteins from hydrophilic polymers are available. Longterm release of peptides from devices that employ cross-linked p(HEMA) as rate-limiting barriers has been reported (Davidson et al, 1988). The use of hydrophilic polymers for protein release is discussed in more detail elsewhere in this volume. 

The objective of this chapter is to review degradable materials, including polymers, and the resulting delivery systems fabricated from them that are usefid for the delivery of proteins and peptides. Owing to the diverse nature of the subject area, we have chosen to divide the chapter into sections on hydrophobic synthetic polymers, hydrophilic polymeric biomaterials, and hydrophobic nonpolymeric biomaterials. Each section seeks to briefly highlight ftie chemist and characteristics of the polymer or matrix and provide recent examples of their use in the delivery of proteins. 

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