Polyanhydrides poly polymers

Recently, a new polyanhydride, poly(fatty acid-sebacic acid), has been synthesized. This polyanhydride uses hydrophobic dimers of erucic acid. Some of its physical properties relevant to the fabrication of drug delivery devices are also improved over those of the other anhydrides based on CPP lower melting temperature, higher solubility in solvents, and higher mechanical strength. The erosion of the polymers is dependent on... 

Degradable, synthetic polymers that are commonly known in the medical field include poly(a-hydroxy esters), poly(fi-caprolactone), poly(ortho esters), polyanhydrides, poly(3-hydroxy butyrate), polypho-sphazenes, polydioxanones, polyoxalates, and poly(amino acids). 

Several excellent reviews have recently been published that describe the broad field of degradable biomedical polymers [9,10]. Well-known hydrolytically degradable polymers developed or being developed for biomedical used include homo- and copolymers of polyamides (usually derived from amino adds), polyesters, polyanhydrides, poly(ortho ester)s, poly(anfido amines), and poly(P-amino esters). This chapter is focused on polyacetals, which... 

Photo-cross-linkable synthetic polymers can be summarized under seven main groups polyanhydrides, poly (ethylene glycol) (PEG), poly(propylene fumarates) (PPFs), poly (a-hydroxy esters), poly(vinyl alcohol) (PVA), poly (P-amino esters), and miscellaneous polymers. Photo-cross-linkable natural polymers include collagen and gelatin and polysaccharides. The details of these systems and their applications are given in Section 9.22.3. 

Key words bioresorbable medical polymers, aliphatic polyesters, polyanhydrides, poly(ortho esters), polyphosphazenes, poly(amino acids), polyalkylcyanoacrylates, poly(propylene fumarate), poloxamers, poly(p-dioxanone), polyvinyl alcohol. 

In addition to polyesters, other types of biodegradable polymers such as polyurethanes, polyanhydrides, poly(amino acids), poly(vinyl alcohol), and poly(ester amide), are generally processable by conventional processing techniques for plastics. Their physical properties can be expected to be comparable, and sometimes can be used to supplement biodegradable polyesters. Although these polymers are more likely used in niche applications or incorporated with other polymers by making composite materials, they obviously provide more material choices in the design and manufacture of various biomedical products. 

There are many polymers that are suitable for the production of nanoparticles employed for drug delivery, which can generally be divided into two groups natural polymers, e.g., polysaccharides (chitosan), proteins (albumin, gelatin), as well as synthetic polymers, e.g., polyesters (poly(lactic add), poly(glycolic add), poly(hydroxy butyrate), poly-e-caprolactone, poly-p-malic add, poly(dioxanones)) polyanhydrides (poly(adipic add)) polyamides (poly(amino acids)) phosphorous-based polymers (polyphosphate) poly(cyano acrylates) polyurethanes polyortho esters and polyacetals. Extreme attention has to be paid to the biodegradability and biocompatibility of the polymers. It is essential that polymers used for medical applications are not detrimental for the tissue or cells and that they can be easily decomposed into simple harmless molecules and eliminated by the human body [ 18-22]. 

The ability to undergo biodegradation producing nontoxic by-products is a useful property for some medical applications. Biodegradable polymers [71] have been formulated for uses such as sutures, vascular grafts, drug delivery devices, and scaffolds for tissue regeneration, artihcial skin, orthopedic implants, and others. The polymers commonly known in the medical field for such applications include poly(a-hydroxy esters), poly(e-caprolactone), poly(ortho esters), polyanhydrides, poly(3— hydroxybutyrate), polyphosphazenes, polydioxanones, and polyoxalates (see Chapter 2 of Industrial Polymers, Specialty Polymers, and Their Applications). 

A considerable number of non-cross-linked aromatic and heterocyclic polymers has been produced. These include polyaromatic ketones, aromatic and heterocyclic polyanhydrides, polythiazoles, polypyrazoles, polytriazoles, poly-quinoxalines, polyketoquinolines, polybenzimidazoles, polyhydantoins, and polyimides. Of these the last two have achieved some technical significance, and have already been considered in Chapters 21 and 18 respectively. The most important polyimides are obtained by reacting pyromellitic dianhydride with an aromatic diamine to give a product of general structure (Figure 29.17). 

Implants in the rabbit corneas exhibited no observable inflammatory characteristics over a period of 6 weeks. Compared to other previously tested polymers, the inertness of these polyanhydrides rivals that of the biocompatible poly(hydroxyethyl methacrylate) and ethylene-vinyl acetate copolymer. Histological examination of the removed corneas also revealed the absence of inflammatory cells (21)... 

Polyester synthesis was carried out hy insertion-dehydration of glycols into polyanhydrides using lipase CA as catalyst (Scheme 6). The insertion of 1,8-octanediol into poly(azelaic anhydride) took place at 30-60°C to give the corresponding polyester with molecular weight of several thousands. Effects of the reaction parameters on the polymer yield and molecular weight were systematically investigated. The dehydration reachon also proceeded in water. The reaction behaviors depended on the monomer structure and reaction media. 

Polyanhydrides based on unsaturated and fatty acid-derived monomers are shown in Table III. Poly(fumaric acid) (PFA) was fist synthesized by Domb et al. (1991) by both melt polycondensation and solution polymerization. The copolymer of fumaric acid and sebacic acid (P(FA-SA)) has been synthesized and characterized (Domb et al., 1991 Mathiowitz et al., 1990b). The mucoadhesive properties of this polymer... 

Fatty acids have also been converted to difunctional monomers for polyanhydride synthesis by dimerizing the unsaturated erucic or oleic acid to form branched monomers. These monomers are collectively referred to as fatty acid dimers and the polymers are referred to as poly(fatty acid dimer) (PFAD). PFAD (erucic acid dimer) was synthesized by Domb and Maniar (1993) via melt polycondensation and was a liquid at room temperature. Desiring to increase the hydrophobicity of aliphatic polyanhydrides such as PSA without adding aromaticity to the monomers (and thereby increasing the melting point), Teomim and Domb (1999) and Krasko et al. (2002) have synthesized fatty acid terminated PSA. Octanoic, lauric, myristic, stearic, ricinoleic, oleic, linoleic, and lithocholic acid acetate anhydrides were added to the melt polycondensation reactions to obtain the desired terminations. As desired, a dramatic reduction in the erosion rate was obtained (Krasko et al., 2002 Teomim and Domb, 1999). 

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... 

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