Polyanhydrides biodegradability

Dang, W. Daviau, T. Brem, H. Morphological characterization of polyanhydride biodegradable... 

Mallapragada et al. have prepared polyanhydrides, biodegradable polymers, from aliphatic and aromatic diacids under the action of microwave irradiation (Scheme 14.25) [54]. The reactions were performed in a household microwave oven. For this purpose, 0.49 mmol aliphatic or aromatic acid were mixed with 2.95 mmol acetic anhydride and irradiated at full power in a sealed borosilicate vial for 2 min. The anhydride was then removed by evaporation and the vial was irradiated for another 5 to 25 min. It was found that by use of this method it was possible to obtain polymers with number-average molecular weights (1700 to 11 300 g mol ) rather similar to those obtained under conventional conditions while reducing the reaction time from hours to 6-20 min. It was also possible to prepare copolymers of seba-cinic acid prepolymer and l,6-bis-(p-carboxyphenoxy)hexane. 

Mathiowitz, E., Leong, K., and Langer, R., Macromolecular drug release from biodegradable polyanhydride microspheres, 12th Int. Symp. Control. Rel. Bioact. Mater., 183-184, 1985. 

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... 

L Shieh, J Tamada, Y Tabata, A Domb, R Langer. Drug release from a new family of biodegradable polyanhydrides. J Controlled Release 29 73-82, 1994. 

Vogel BM, Cabral IT, Eidelman N, Narasimhan B, Mallapragada SK (2005) Parallel synthesis and high throughput dissolution testing of biodegradable polyanhydride copolymers. J Comb Chem 7 921-928... 

Biodegradable polymers, both synthetic and natural, have gained more attention as carriers because of their biocompatibility and biodegradability and therewith the low impact on the environment. Examples of biodegradable polymers are synthetic polymers, such as polyesters, poly(orfho-esters), polyanhydrides and polyphosphazenes, and natural polymers, like polysaccharides such as chitosan, hyaluronic acid and alginates. 

Shieh L, Tamada J, Chen I, Pang J, Domb A, Langer R. Erosion of a new family of biodegradable polyanhydrides. J Biomed Mater Res 1994 28 1465-1475. 

Gopferich A. Biodegradable polymers polyanhydrides. In Mathiowitz E, ed. The Encyclopedia of Controlled Release. New York Wiley, 1999 60-71. 

Several review articles on biodegradable polymers and polyesters have appeared in the literature [12-22]. Extensive studies have been carried out by Al-bertsson and coworkers developing biodegradable polymers such as polyesters, polyanhydrides, polycarbonates, etc., and relating the structure and properties of aliphatic polyesters prepared by ROP and polycondensation techniques. In the present paper, the current status of aliphatic polyesters and copolyesters (block, random, and star-shaped), their synthesis and characterization, properties, degradation, and applications are described. Emphasis is placed primarily on aliphatic polyesters derived by condensation of diols with dicarboxylic acids (or their derivatives) or by the ROP of cyclic monoesters. Polyesters derived from cyclic diesters or microbial polyesters are beyond the scope of this review. 

As pointed out by Heller (2), polymer erosion can be controlled by the following three types of mechanisms (1) water-soluble polymers insolubilized by hydrolytically unstable cross-links (2) water-insoluble polymers solubilized by hydrolysis, ionization, or protonation of pendant groups (3) hydrophobic polymers solubilized by backbone cleavage to small water soluble molecules. These mechanisms represent extreme cases the actual erosion may occur by a combination of mechanisms. In addition to poly (lactic acid), poly (glycolic acid), and lactic/glycolic acid copolymers, other commonly used bioerodible/biodegradable polymers include polyorthoesters, polycaprolactone, polyaminoacids, polyanhydrides, and half esters of methyl vinyl ether-maleic anhydride copolymers (3). 

Polyanhydrides, such as poly[bis(p-carboxyphenoxy)propane sebacic acid] copolymers (Figure 4.14), are also used for the fabrication of biodegradable implants. Polymer degradation occurs via hydrolysis, the biscarboxyphenoxypropane monomer is excreted in the urine and the sebacic acid monomer is metabolized by the liver and is expired as carbon dioxide via the lung (Figure 4.14). 

Gliadel is a biodegradable polyanhydride implant composed of poly[bis(p-carboxyphenoxy) propane sebacic acid] in a 20 80 monomer ratio, for the delivery of carmustine. The implant is indicated in the treatment of recurrent glioblastoma multiforme (GBM) which is the most common and fatal type of brain cancer. 

Kipper, M. J., Wilson, J. H., Wannemuehler, M. J., and Narasimhan, B. (2006), Single dose vaccine based on biodegradable polyanhydride microspheres can modulate immune response mechanism,/. Biomed. Mater. Res. Part A, 76,798-810. 

These polyanhydrides all possessed suitable properties including low melting points (60-82°C), biodegradability and pliability. These polyanhydrides were able to retain both hydrophilic (5FU) and hydrophobic (triamcinolone) drugs. The release of 5FU continued for almost 2 weeks and of triamcinolone for 3 weeks. 

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. 

---