Polyanhydrides applications

A major part of this chapter will review recent developments in the chemistry and properties of polyanhydrides, which includes new synthetic methods, new polymeric structures, and in depth characterization of polyanhydrides. The degradation and drug release properties and applications that were not reviewed previously are included. A review article by the same authors concentrating on polyanhydride applications and toxicity is in preparation [6]. 

Applications of Polyanhydrides have been reviewed [1, 22]. A comprehensive review on polyanhydride applications is in preparation [6],... 

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. 

Several new series of polyanhydrides with advantageous properties for a variety of applications were also synthesized (8). The first ai e aliphatic-aromatic homopolyanhydrides of the structure... 

We have already mentioned a few of the polyanhydride chemistries that have been studied in drug delivery applications. Tables II through VII present some of the polyanhydrides that have been explored for drug... 

The chemistry of polyanhydrides is by no means limited to the categories discussed in the preceding sections. A brief review of some of the additional chemistries that have recently been synthesized follows with a mention of their potential for application in drug delivery. 

It is important to characterize the thermal properties of polyanhydrides that are proposed for drug delivery applications, as changes in crystallinity... 

Biocompatibility is an essential property of new biomaterials for drug delivery. Biocompatibility is always assessed with respect to specific applications and may be assessed with respect to cytotoxicity, allergic responses, irritation, inflammation, mutagenicity, teratogenicity, and carcinogenicity (Katti el al., 2002). The reviews by Katti et al. (2002) and Domb et al. (1997) provide good discussions on the biocompatibility studies that have been conducted with polyanhydrides over the past two decades. 

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. 

The development of new polyanhydrides has sparked researchers to developed new device fabrication and characterization techniques, instrumentation, and experimental and mathematical models that can be extended to the study of other systems. The growing interest in developing new chemistries and drug release systems based on polyanhydrides promises a rich harvest of new applications and drug release technologies, as well as new characterization techniques that can be extended to other materials. Future endeavors will likely focus on multicomponent polyanhydride systems, combining new chemical functionalities to tailor polyanhydrides for specific applications. 

Polyanhydrides were first developed by Carothers and coworkers in the early 20th century for applications in the textile industry. The interest in these polymers waned soon thereafter because of their instability. However it was the poor hydrolytic stability that made these polymers attractive candidates for drug delivery applications (17). 

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. 

Aliphatic polyesters are, together with polycarbonates, polyanhydrides, and poly(amino acids), the most well-known synthetic hydrolyzable polymers. They are often prone to degradation but are at the same time usually not good enough for technical applications. A renewed interest in aliphatic polyesters has resulted in developing new materials important in the biomedical and ecological fields. 

Polyanhydrides Polyanhydrides have a hydrophobic backbone with a hydrolytically labile anhydride linkage. These polymers widely vary in chemical composition and include aliphatic, aromatic, and fatty acid-based polyanhydrides. The rate of degradation depends on the chemical composition of the polymer. In general, aliphatic polyanhydrides degrade more rapidly than the aromatic polymer. Hence, copolymer blends with varying ratios of aliphatic-to-aromatic polyanhydrides can be synthesized to suit specific applications. 

Polyanhydride Nanoparticles Polyanhydrides have been more commonly used to prepare microparticles than nanoparticles. However, the technology is adaptable for nanoparticles. The transfection efficiency of firefly luciferase DNA was enhanced when delivered in nanoparticles prepared from polyanhydride-lactic acid blends, demonstrating the potential application in gene delivery [120], The degradation and elimination of polyanhydrides have been reviewed [97], In vivo, the anhydride bond degrades to form diacid monomers that are eliminated from the body. 

Fatty acids have been used previously in the development of polymers for biomedical applications as they are considered to be inert, inexpensive and biocompatible. The main fatty acids which are used as a base for synthesis of biomedical polymers (polyanhydrides) are stearic acid (/), erucic acid (C22 unsaturated fatty acid) dimer (2), bile acid dimer (i), ricinoleic acid 4) and other fatty acids (5), middle long carbon chain (C12 - 15) dibasic acids, such as dodecanedioic, brassylic acid, tetradecandioic acid and pentadecandioic acid (/). 

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... 

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