Polyanhydrides types

The second type of polymer, unsaturated polyanhydrides of the structure [-(OOC-CH=CH-CO)x-(OOC-R-CO)y-]n, have the advantage of being able to undergo a secondary polymerization of the double bonds to create a crosslinked matrix. This is important for polymers requiring great strength, for instance. These polymers were prepared from the corresponding diacids polymerized either by... 

The property that makes polyanhydrides unique is their surface hydrophobic-ity. Due to this high hydrophobicity, polyanhydride matrices do not facilitate water absorption. Consequently, hydrolytic degradation is restricted to the surface—a property that is termed as surface erosion. This type of degradation allows for zero-order release of drugs, i.e., the drug release profile is independent of the residual concentration of the drug in the matrix. 

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). 

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. 

In contrast to bulk-eroding PLA/PLGA polymers, the polyanhydride undergoes surface erosion. The thin-disk type morphology of the wafer confers a high surface-to-volume ratio on the implant, so that the total surface area of the implant is kept almost constant over the time of polymer degradation, which facilitates a constant release of carmustine with time. 

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. 

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. 

Recently formation of the adduct II of benzene and maleic anhydride under the influence of gamma radiation was reported (14). The adduct is only a minor product of the reaction, corresponding to about 4% of the maleic anhydride spent. The main product is a mixture of polyanhydrides. These can be considered to arise through a free radical chain similar to the one yielding adducts of Type I. 

The erosion in polyanhydride matrices has been reported to be purely surface of the heterogeneous type, and the results of this study support the past observation [82]. No lag time for drug release was found, as observed also for poly-lactic acid and poly-lactic acid-glycolic acid, which have been known to undergo bulk erosion [79]. In addition, fit of the data to Eqs. (1) and (2) (which have been derived for a surface eroding polymer), confirm the surface eroding nature of the polyanhydrides. 

A second method to prepare polyanhydride microspheres—via solvent removal—has also been developed. Polyanhydrides composed of the following diacids were used sebacic acid (SA), bis(p-carboxyphenoxypropane (CPP), and dodecanedioic acid (DD). Drug release was affected by polymer composition, physical properties of the microspheres, and type of drug. The potential for injectable microspheres (size range 1-300 jum) made of CPP-SA (50 50) for the controlled release of insulin was assessed. Both 5% and 10% w/w insulin loaded microspheres were prepared. The best clinical response was produced by 10% loaded microspheres, which... 

In addition to ester-based polyesters, a great deal of research activity has been directed to other types of absorbable polymers, but the clinical relevance of their properties practically halted their evolution beyond the exploratory phase. Typical examples of these polymers have been covered in a review by Shalaby and include those based on polyanhydrides, polyortiioesters, poly-phosphazenes, and certain polyamidoesters. ... 

With the development of absorbable cyanoacrylate systems, the classification of synthetic, absorbable polymers into the traditional heterochain polymers (e.g., polyesters and polyanhydrides) and less-conventional homochain polymers (e.g., cyanoacrylate polymers) became inevitable. " Meanwhile, since ester-based systems are most important among both the heterochain-and homochain-type synthetic, absorbable polymers, they are given special attention in this chapter. 

The use of lipids, including lipid-protein membranes, concentric lipid manbranes, and submicron ultrathin lipid membranes is another common approach. Biodegradable synthetic polymers offer another approach. The first one used was polylactide. Many types of polylactides and poly-glycolic acids are now used for artificial cells. Other synthetic biodegradable polymers, such as polyanhydride, also are used. The use of biodegradable artificial cells has become an active field. 

The melting point, as determined by differential scanning calorimeter, of these aromatic polyanhydrides is mnch higher than aliphatic polyanhydrides. The melting point of aliphatic-aromatic copolyanhydrides is proportional to aromatic content. For this type of copolymers, there is characteristically a minimnm between 5 and 20mol% of lower-melting component. The introdnction of fatty acids in the copolymer chain lowers the melting point as compared to that of bulk polymer [14]. 

ROP offers an alternate approach to the synthesis of polyanhydrides used for medical applications. Albertsson and coworkers prepared adipic acid polyanhydride from cyclic adipic anhydride (oxepane-2,7-dione) using cationic (e.g., AICI3 and BFjTCjHj) ), anionic (e.g., CHjCOO K and NaH), and coordination-type inhibitors snch as stannous-2-ethylhexanoate and dibutyltin oxide [24,25]. ROP takes place in two steps (1) preparation of the cyclic monomer and (2) polymerization of the cyclic monomers [26]. 

Various biocompatibiUty studies reported on several polyanhydrides have shown them to be nonmutagenic and nontoxic. In vitro tests measuring teratogenic potential were also negative. Growth of two types of mammahan cells in tissue culture was also not affected by the polyanhydride... 

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