Fatty acid polyanhydrides

Transparent and flexible films of fatty acid polyanhydrides were reported with a tensile strength of 4-19MPa and elongation at break in the range of 77-115%. Thus, introduction of nonhnear fatty acid structures in polyanhydrides provides hydrophobicity and flexibility to the polymers. 

Table 3. Physical Properties of Fatty Acid Polyanhydrides ...

M Maniar, AJ Domb, A Haffer, J Shah. Controlled-release of a local anesthetic from fatty-acid dimer based polyanhydride. J Controlled Release 30 233-239, 1994. 

Polyanhydrides from Unsaturated and Fatty Acid-derived Monomers... 

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). 

Pharmaceutical research has to date been focused on polyanhydrides derived from sebacic acid (SA) and its copolymers with bis(p-carboxyphenoxy)propane (CPP) [75,113,115,119]. More recently, a new class of polyanhydrides was presented, containing fatty acid dimers (FAD) [ 116,118,258]. Erosion characteristics, microsphere preparation, pH-dependence, release rates, morphology, and in vivo performance of polyanhydrides from SA, CPP, and FAD have been intensely studied [75, 111-115,117, 119, 258-260]. Other unsaturated polyanhydrides have been derived from ricinoleic acid [261] and ricinoleic acid half-es-... 

Several combinations of monomers used to prepare polyanhydrides are classified as aliphatic, aromatic, aliphatic-aromatic, amine-based, and fatty acid-based polyanhydrides. The structures of these monomers determine... 

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... 

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. 

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 (/). 

Polyanhydrides prepared from fatty acids are good candidates for the delivery of hydrophilic drugs due to the desired hydrophobicity of the natural fatty acids in the main chain of the polyanhydrides 11). These polyanhydrides have two series of acid monomers one has longer carbon chain, such as dimer erucic or oleic acid another has shorter carbon chain, such as sebacic acid (2). Fatty acids can be incorporated into the polymer chain by one of two ways by... 

The second approach was applied in the synthesis of fatty acid terminated polyanhydrides. Polyanhydrides based on sebacic acid, and terminated with oleic, stearic, linoleic or lithocholic acid, or combinations of several fatty acids were synthesized 21). The general structure of fatty acid terminated polyanhydrides is shown in Figure 1. 

Figure I. Fatty acid terminated polyanhydrides (reproducedfrom reference 7) R=Oleic, stearic, linoleic, lithocholic acids.

The incorporation of fatty acids into a polyanhydride chain was investigated using two fatty acids lithocholic acid and ricinoleic acid. Lithocholic acid containing polyanhydrides (Figure 2) were prepared by two step synthesis. Polyanhydrides reached molecular weights of 21000-115000 Da, depending on the polymer composition. Release of model drugs from these polymers showed sustained release of 5FU for almost 3 weeks and triamcinolone for 4 weeks (22). 

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. 

Polyanhydrides were synthesized from dimer and trimer of unsaturated fatty acids. The dimers of oleic acid and erucic acid, prepared by radical coupling via... 

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]. 

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