Polyanhydrides surface-eroding polymers

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. 

In addition, polyanhydrides have a predicable release rate as they are surface-eroding polymers [194],... 

Polyanhydrides form a class of surface-eroding polymers that have been extensively studied solely for biomedical applications. Although the first synthesis of polyanhydrides was reported as early as 1909, the low hydrolytic stability of aliphatic anhydrides coupled with the low molecular weight of many of these polymers barred them from any industrial application until 1980, when they were suggested as ideal candidates for drug-delivery applications. Various polymerization techniques have been developed for the synthesis of very-high-molecular-weight polymers. 

The past two decades have produced a revival of interest in the synthesis of polyanhydrides for biomedical applications. These materials offer a unique combination of properties that includes hydrolytically labile backbone, hydrophobic bulk, and very flexible chemistry that can be combined with other functional groups to develop polymers with novel physical and chemical properties. This combination of properties leads to erosion kinetics that is primarily surface eroding and offers the potential to stabilize macromolecular drugs and extend release profiles from days to years. The microstructural characteristics and inhomogeneities of multi-component systems offer an additional dimension of drug release kinetics that can be exploited to tailor drug release profiles. 

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. 

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. 

Thus, considerable effort has been devoted to the development of polymers that are able to erode by a well controlled surface hydrolysis process. Dominant among these are polyanhydrides [2] and poly (ortho esters) [3]. 

---