Synthetic hydrophobic degradable polymers

Poly(lactic acid), Poly(glycolic add), and Their Copolymers 

Macromolecules and peptides including bovine semm albumin (BSA Bodmer et a/., 1992 Cohen eta/., 1991 Wang eta/., 1991 Sah and Chien, 1993), human serum albumin (Hora eta/., 1990), calcitonin (Lee eta/., 1991), 

Early work in this area was published in several articles by Sanders and co-workers, who described the use ofpoly(D,L-lactide-co-glycolide) (PLGA) microcapsules for the delivery of the peptide nafarelin acetate, an LHRH analog [(D-Nal(2) Aza-Gly )-LHRH Syntex] (Anik et al, 1984 Sanders et al, 1984, 1985, 1986). Microcapsules were produced by a coacervation microencapsulation technique, and the release of the peptide was shown to be predominately triphasic (Fig. 1)—high initial release lasting for several hours, followed by a period of low or limited release, and finally several days 

F ure 1. In vitro release of nafarelin fiom 45 56 poly(DHactide-co-glycolide) microspheres. Conditions Agitated in ethanolic phosphate buffer (pH7.4) at 37°C. (After Sanders et al, 1985.) 

Okada and co-workers (1988,1989,1991) and Ogawa etal. (1988) have also described a 75 25 PLGA microencapsulated 30-day release system for the delivery of another LHRH analog leuproUde acetate [(D-Leu , Pro NEt)-LHRH Lupron Depot , Takeda-Abbott], Their results indicate that a single injection of microcapsules maintains constant and effective serum levels of the analog for one month. Sufficient therapeutic efficacy in the treatment of advanced prostatic cancer has also been shown for leuprolide acetate, and the product has recently been approved for use by the U.S. Food and Drug Administration (Lupron Depot , 7.5mg PDR, 1994). This treatment has also shown to cause a dramatic regression of 

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The instability of high molecular weight synthetic polymers was one of the considerations in pioneering the synthesis of the hydrophobically modified styrene-maleic acid copolymers (3). An improved polymer system [that] would not degrade mechanically and [that] would retain [its] viscosity in the presence of electrolytes and heat was required (4). 

Poly(ortho esters) were first developed by the ALZA corporation (Alzamer) in 1970 in order to seek new synthetic polymer for drug delivery applications. These polymers degrade by surface erosion and degradation rates may be controlled by incorporation of acidic or basic excipients. The polymer is hydrophobic enough such that its erosion in aqueous environments is very slow. The unique features of poly(ortho esters), in addition to their surface erosion mechanism, is the rate of degradation for these polymers, pH sensitivity, and glass transition temperatures, which... 

Synthetic polymers include macromolecules formed from monomers by chemical polymerization reactions. Synthetic polymers possess some significant advantages over natural polymers, such as high purity and better reproducibility. The properties of synthetic polymers, such as degradation rate, hydrophobicity and drug release rate, can be manipulated easily by structural modifications or formulation parameters. Synthetic polymers can be modified and functionalized easily and they allow production of tailor-made nanocarriers. These nanocarriers sustain the release of the encapsulated therapeutics over a period of hours to weeks in an adjustable manner. ... 

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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