Biomedical Engineering Reference
In-Depth Information
High hydrolytic reactivity of the anhydride linkage provides an intrinsic advan-
tage in versatility and control of degradation rates. By varying the type of monomer
and their ratios, surface-eroding polymers with degradation times of 1 week to
several years can be designed and synthesized. The hydrolytic degradation rates
can be obtained varying several thousand folds by simple changes in the polymer
backbone and by altering the hydrophobic and hydrophilic balance of the polymer
[5 - 7] . Aliphatic polyanhydrides degrade in a few days, while some aromatic poly-
anhydrides degrade over a few years. Degradation rates of copolymers of aliphatic
and aromatic polyanhydrides vary between these extremes, and this feature of
polyanhydrides gives an opportunity for making a drug delivery system which can
provide the release of drugs for a desired time length of treatment.
3.2
Types of Polyanhydride
Bucher and Slade synthesized aromatic polyanhydrides [8]; however, these were
fi rst explored by Conix after almost 50 years to form fi bers for textile applications
[9] . Hill and Carothers [10, 11] had worked in the 1930s on aliphatic PAs of adipic
and sebacic acid (SA); because of hydrolytic instability, no further development
was carried on these polymers until they were explored by Langer in the 1980s for
drug delivery [1, 12]. Heterocyclic PAs were also developed in the meantime by
Yoda
et al.
with good fi lm and fi ber-forming properties [13]. Once the degradable
and biocompatible nature of PAs was uncovered, various types of copolymers were
prepared thereon and utilized in drug delivery. One of the simplest classifi cations
for PAs can be homo- and hetero-PAs; however, in the development of erodible
materials, the use of copolymers (heteropolymers) is important for their different
erosion rates, enabling the achievement of different target times for release, and
this is possible by using different monomers and their ratio. In most PA copoly-
mers, the aliphatic chain used is composed of polysebacic acid (PSA) and thus
these are classifi ed on the basis of the other part of the copolymer, which in turn
governs the polymer properties. All the polyanhydrides with their representative
chemical structure are shown in Table 3.1 .
3.2.1
Aromatic Polyanhydrides
Aromatic homopolyanhydrides are insoluble in common organic solvents
and melt at temperatures above 200 °C [6, 15]. These properties limit the use of
purely aromatic polyanhydrides, since they cannot be fabricated into fi lms or
microspheres using solvent or melt techniques. Fully aromatic polymers that
are soluble in chlorinated hydrocarbons and melted at temperatures below 100 °C
were obtained by copolymerization of aromatic diacids such as isophthalic acid
( IPA ), terephthalic acid ( TA ), 1,3 - bis(carboxyphenoxy)propane ( CPP ), or 1,3 - bis
(carboxyphenoxy)hexane ( CPH ).
