Polyanhydrides classes

Pharmaceutical research has to date been focused on polyanhydrides derived from sebacic acid (SA) and its copolymers with bis(p-carboxyphenoxy)propane (CPP) [75,113,115,119]. More recently, a new class of polyanhydrides was presented, containing fatty acid dimers (FAD) [ 116,118,258]. Erosion characteristics, microsphere preparation, pH-dependence, release rates, morphology, and in vivo performance of polyanhydrides from SA, CPP, and FAD have been intensely studied [75, 111-115,117, 119, 258-260]. Other unsaturated polyanhydrides have been derived from ricinoleic acid [261] and ricinoleic acid half-es-... 

Fatty acid based biodegradable polymers have many biomedical applications. This short review focuses on controlled drug delivery using two classes of the polymers polyanhydrides and polyesters based on fatty acids as drug carriers. Different polymer types and compositions are summarized showing the potential of these polymers as drug carriers. 

While many different polymer chemistries have been developed for drug delivery applications, only one class of polymer beside the polyesters has received regulatory approval. Gliadel is a thin wafer containing the chemotherapeutic agent carmustine (BCNU) in a polyanhydride polymer matrix. Gliadel received... 

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... 

Historically, polyanhydrides were developed in the textile industry during the first half of the 20th century as alternate fiber materials. " However, the modern polyanhydrides that are currently under investigation as drug delivery platforms represent a novel class of polymer that, unlike the polyesters, has been specifically developed for biodegradable applications. In particular, these polyanhydrides were specifically prepared in attempts to produce surface-eroding dosage forms. 

Today a vast range of BP classes are available, including polyesters, polyamides, polyurethanes, polyureas, polyethers, polyanhydrides, poly(orthoester)s, polypeptides,... 

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. 

There are three major classes of polyanhydrides aliphatic, unsaturated, and aromatic. The chemical structures are shown in Table 1. 

Polyanhydrides are promising as biomaterials because they possess a unique combination of properties that include hydrolytically labile backbone, hydrophobic bulk, and chemistry that can be easily combined with other functional groups to design novel materials. These materials are primarily surface-erodible and offer the potential to stabilize protein drugs and sustain release from days to months. The microstructure characteristics of copolymer systems can be exploited to tailor drug release profiles. The versatility of polyanhydride chemistry promises a new class of drug release systems for specific applications. 

Goepferich, A. Langer, R. The influence of microstructure and monomer properties on the erosion mechanism of a class of polyanhydrides. J. Polym. Sci. A Polym. Chem. 1993, 31, 2445-2458. 

A much more desirable erosion mechanism is surface erosion, where hydrolysis is confined to a narrow zone at the periphery of the device. Then, if the drug is weU-immobihzed in the matrix so that drug release due to diffusion is minimal, the release rate is completely controlled by polymer erosion, and an ability to control erosion rate would translate into an ability to control dmg delivery rate. For a polymer matrix that is very hydrophobic so that water penetration is limited to the surface (thus Hmiting bulk erosion), and at the same time, allowing polymer hydrolysis to proceed rapidly, it should be possible to achieve a drug release rate that is controlled by the rate of surface erosion. Two classes of biodegradable polymers successfully developed based on this rationale are the polyanhydrides [31] and poly (ortho esters) [32], the latter of which is the subject of this chapter. 

The degradation rates for a number of polyanhydrides are available in the literature [1, 82,83], However, recently, a new class of polyanhydrides poly(FAD-SA) have been synthesized from non-linear hydrophobic dimer of oleic acid or erucic acid and relatively hydrophilic sebacic acid. This copolymer can be prepared in various ratios of the monomers to achieve the desired degree of hydrophobicity increasing the percentage of FAD, a more hydrophobic copolymer, is obtained. Another advantage of this copolymer is its ability to be formulated as films, microspheres, and beads [84],... 

Poly(ortho esters) (XVII) contain acid-labile linkages in the polymer backbone. As with the polyanhydrides discussed above, poly(ortho esters) are a class of polymers that can degrade heterogeneously by surface erosion. These polymers lose material from the surface only, while retaining their original geometry. As such, their primary use is in drug delivery. 

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