Polyanhydrides containing

Polycarbonates and polyanhydrides are grouped together, although polycarbonates contain the functionality -0-C(0)-0- in their backbone, and polyanhydrides contain the functionality -C(0)-O- (O)-. Both types of polymers are common in practice. 

Jiang, H.L. Zhu, K.J. Preparation, characterization and degradation characteristics of polyanhydrides containing poly(ethylene glycol). Polym. Int. 1999, 48, 47-52. 

B.M. Vogel, S.K. Mallapragada, Synthesis of novel biodegradable polyanhydrides containing aromatic and glycol functionality for tailoring of hydrophilicity in controlled dmg delivery devices. Biomaterials 26 (2005) 721-728. 

Aromatic polyanhydrides containing aromatic groups since homopolymers belonging to this category melt at temperatures above 200 °C and caimot be properly processed, copolymers obtained from different aromatic diacids are commonly employed. 

For many drug delivery applications, the preferred method of delivery of the dosage form is by injection. For controlled release applications, the most frequently used approach to allow this method of administration is to prepare microspheres of the polymer containing the drug to be delivered. Several different techniques have been developed for the preparation of microspheres from polyanhydrides. 

Once the blood glucose values in the treated animals had returned to the high, diabetic levels, a second injection of insuUn-containing microspheres again reduced these levels to normal for about 5 more days. It is therefore possible to incorporate labile biological products into the polyanhydrides and to release them in a biologically active form. At the same time, this release can be sustained over a period of time in a controlled fashion. 

Two other series of biodegradable polymers that depend upon chain degradation are the polyanhydrides and the polyorthoesters. Both of these polymers contain hydrophobic units linked together along the polymer chain by functional... 

The synthesis of poly(anhydride-co-amide)s (Table VII) of various chemistries was pursued by Hartmann and Schulz (1989) as a means of improving biocompatibility and extending the degradation times of polyanhydrides. This work also contains calorimetry data on the thermal transitions and spectroscopic characterization. 

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-... 

Chemically-Controlled Systems. In these systems, the polymer matrix contains chemically-labile bonds. On exposure to water or enzymes the bonds hydrolyze, erode the three dimensional structure of the polymer and release the incorporated reagent into the surrounding medium. Depending on the polymer used, the erosion products may act as interferences, such as by altering the pH of the solution. Examples of these systems are polyglycolic acid (PGA) and a polyglycolic acid - polylactic acid (PGA/PLA) copolymer. PGA hydrolyzes to hydroxyacetic acid, and PGA/PLA hydrolyzes to lactic acid and hydroxyacetic acid. Other chemically-controlled systems are based on polyorthoesters, polycaprolactones, polyaminoacids, and polyanhydrides. 

A commercial product based on polyanhydrides is Gliadel wafer containing carmustine, an antitumor agent. The wafer, 1.45 cm in diameter and 1 mm thick, is made of poly[bis-(/>carboxyphenoxy) propane sebacic acid] in an 80 20 molar ratio. 

The incorporation of fatty acids into a polyanhydride chain was investigated using two fatty acids lithocholic acid and ricinoleic acid. Lithocholic acid containing polyanhydrides (Figure 2) were prepared by two step synthesis. Polyanhydrides reached molecular weights of 21000-115000 Da, depending on the polymer composition. Release of model drugs from these polymers showed sustained release of 5FU for almost 3 weeks and triamcinolone for 4 weeks (22). 

Figure 2. Lithocholic acid containing polyanhydrides (reproduced from...

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... 

As with PLA or PLG carriers, the application of either polyanhydride or polyorthoester polymers for 5-FU sustained release in glaucoma treatment or PVR has been investigated. Using compression techniques, polyanhydride devices constructed from combinations of(p-carboxyphenoxy)alkanes with sebacic acid have been produced. Disk or T-shaped polyanhydride devices containing between 10 and 20%i 5-FU prolonged lOP reduction and bleb survival in filtration models or... 

Figure 8.36 Theoretical representation of a polymer matrix changes during erosion (dark pixels = nondegraded areas, white pixels = degraded areas), where (a rate constant) = 2.7 x 1 0 s for a sample containing 50% polyanhydride CPP.

Poly(anhydrides) are polymers containing the group -C(0)-0-C(0)- in their backbone. Several polyanhydrides such as poly(oxyisophthaloyl), poly(oxycarbonyl-1,4-phenylene methylene-1,4-phenylene carbonyl), poly(oxycarbonyl-1,4-phenylene isopropylidene-1,4-phenylene carbonyl), and poly(oxycarbonyl-1,4-phenylene isobutylidene-1,4-phenylene carbonyl) were synthesized with the expectation of good biodegradability. They do have good hydrolytic stability as opposed to aliphatic polyanhydrides [1]. The structures of these polymers are shown below. 

A separate polyanhydride system has also been investigated for the treatment of osteomyelitis, a bone infection typically caused by bacteria. ° Copolymer implants (50 50 FAD SA) containing gentamicin were tested in the backs of rats, in the infected tarso-crural joints of horses, and in humans with infected prosthetic hips or knees. In all the cases, the local delivery of gentamicin was successful and the systemic exposure to the drug was avoided. 

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