Poly Anhydrides

Poly(anhydrides). Poly(anhydrides) are another class of synthetic polymers used for bioerodible matrix, dmg dehvery implant experiments. 

An example is poly(bis(p-carboxyphenoxy)propane) (PCPP) which has been prepared as a copolymer with various levels of sebacic anhydride (SA). Injection molded samples of poly (anhydride) / dmg mixtures display 2ero-order kinetics in both polymer erosion and dmg release. Degradation of these polymers simply releases the dicarboxyhc acid monomers (54). Preliminary toxicological evaluations showed that the polymers and degradation products had acceptable biocompatibiUty and did not exhibit cytotoxicity or mutagenicity (55). 

In order to become useful dmg delivery devices, biodegradable polymers must be formable into desired shapes of appropriate size, have adequate dimensional stability and appropriate strength-loss characteristics, be completely biodegradable, and be sterilizahle (70). The polymers most often studied for biodegradable dmg delivery applications are carboxylic acid derivatives such as polyamides poly(a-hydroxy acids) such as poly(lactic acid) [26100-51-6] and poly(glycolic acid) [26124-68-5], cross-linked polyesters poly(orthoesters) poly anhydrides and poly(alkyl 2-cyanoacrylates). The relative stabiUty of hydrolytically labile linkages ia these polymers (70) is as follows ... 

Poly (anhydrides) based on aliphatic-aromatic diacids. Macromolecules. In Press. 

Tomayo et al. have also reported that poly(anhydride) nanoparticles act as agonists of various TLRs. The nanoparticles were useful as Thl adjuvants in immunoprophylaxis and immunotherapy through TLR exploitation [120],... 

Tamayo I, Irache JM, Mansilla C et al (2010) Poly(anhydride) nanoparticles act as active Thl adjuvants through Toll-like receptor exploitation. Clin Vaccine Immunol 17 1356-1362... 

Another class of PSA-fatty acid-based copolymers has been synthesized from the ricinoleic acid and ricinoleic half-esters with maleic and succinic anhydride, poly(sebacic-co-ricinoleic acid maleate), poly(sebacic-co-ricinoleic acid succinate), and poly(sebacic-co-12-hydroxystearic acid succinate) (P(SA-RAM), P(SA-RAS), and P(SA-HSAS)) (Krasko et al., 2003 Teomim et al., 1999). These syntheses result in poly(anhydride-co-esters). 

Poly(anhydride-co-ester)s and Poly(anhydride-co-ether)s... 

Poly(anhydride-co-ester)s (Table VI) were suggested as potential polymers for drug delivery and synthesized by Pinther and Hartmann (1990),... 

Erdmann and Uhrich (2000 Erdmann et al., 2000) recently synthesized novel poly(anhydride-co-ester)s containing salicylic acid in the backbone, by melt polycondensation of the disalicylic acid ester of sebacic acid, poly[bis(o-carboxyphenoxy)sebacate] (PCPS) and the copolymer P(CPH-CPS). The release of salicylic acid (the active form of aspirin) from the former was studied in vitro and from the latter was studied in vivo (Erdmann and Uhrich, 2000 Erdmann et al., 2000). Similar polymers that release 5-amino salicylic acid, and p-nitro salicylic acid have been prepared... 

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. 

Jiang and Zhu (2001) became interested in synthesizing additional polyanhydrides with fluorescence after their discovery of the fluorescent properties of PCPS. They synthesized the series of poly(anhydride-co-amide)s poly p-[carboxyphenoxy(ethyl/propyl/butyl)formamido]benzoic anhydride (PCEFB, PCPFB, and PCBFB) (Jiang et al., 2001c). Only the ethyl polymer emitted strong fluorescence, which was consistent with their previous study of the poly(anhydride-co-ester)s of similar chemistry... 

Staubli et al. (1991) offer an in depth analysis of the effects of sequence distribution on the Tg of poly(anhydride-co-imide)s and discuss the experimental results with respect to several applicable theoretical models... 

Molecular weight may also affect the erosion rate. Table IX shows the degradation rate of a representative poly(anhydride-co-urethane), a poly(anhydride-co-amide), and a poly(anhydride-co-ester) of different molecular weights (Hartmann et al., 1993). For all of these polymers reported, the erosion rate decreases as the molecular weight increases. 

The simplest model for pure erosion control with kinetics dominated by a single rate constant and uniformly distributed drugs was described by Hopfenberg (1976). This model says nothing about the various physical phenomena that contribute to erosion, and therefore fails to describe drug release profiles from many poly anhydride systems. Below we classify some of the models that can be found in the literature. 

Erdmann et al. (2000) report the fabrication of devices for the localized delivery of salicylic acid from the poly(anhydride-co-ester)s mentioned in Section II.C. A unique feature of this drug delivery system is that the drug compound is part of the polymer backbone. Devices were implanted intraorally and histopathology was reported (Erdmann et al., 2000). Chasin et al. (1990) review fabrication and testing of implantable formulations for other drugs including angiogenesis inhibitors for treatment of carcinomas and bethanechol for the treatment of Alzheimer s disease. 

Fu et al. (2002) report the optimization of a fabrication procedure for microspheres based on the poly( anhydride-co-ether) P(SA-EG). The microspheres are fabricated by solvent removal process that produces a porous structure with densities in the range of 0.344 and 0.077 g cm-3 and sizes that are optimized for delivery to the deep lung by inhalation (Fu et al., 2002). An appropriate in vitro cell culture model for characterization of the particle-epithelia system was also developed (Fiegel et al., 2003). 

Figure 1. Polymer synthesis scheme for crosslinked poly anhydrides.

Figure 2. Structure of diacid molecules that can be functionalized to create crosslinked poly anhydride networks.

Polyammonium-containing ligands, 24 44 Polyammonium macropolycycles, 76 780 Polyampholytes, 20 475 479 solution properties of, 20 479 synthesis of, 20 477- 478 Poly(anhydrides), bioresorbable polymers, 3 740... 

Alternatively, monolith-supported second generation Crubbs catalysts containing unsaturated (e.g. IMes) or saturated (e.g. SIMes) NHCs [5] can be prepared by a synthetic protocol summarized in Scheme 8.9. Surface-derivatization of a monolith was carried out with 7-oxanorborn-2-enedicarboxylic anhydride followed by conversion of the grafted poly(anhydride) into the corresponding poly-silver salt. 

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