Biomedical Engineering Reference
In-Depth Information
solubility of FAD, the erosion zone mainly consisted of a semisolid mixture of
FAD and FAD salts, instead of porous erosion zone. The semisolid layer forms a
permeation barrier and SA acid was found to precipitate inside the erosion zone;
this ultimately leads to slow release of SA as well as drug. Later polyanhydrides
based on RA were reported to undergo sharp decreases in molecular weight during
fi rst 24 h of erosion
in vitro
and lost 40% of their anhydride bonds in 48 h [16].
Polyanhydride chains terminated with linear fatty acid like lauric, oleic, or stearic
acid also show exponential loss of molecular weight and erosion behavior similar
to RA-based polymer [18]. The increase in amount of fatty acid and the chain
length induced the bulk erosion properties of polyanhydrides [92]. The photo-
crosslinked polyanhydride obtained from MSA, MCPP, and 1,6- bis - carboxyphe-
noxyhexane dimethacrylate showed linear erosion profi les, when eroded
in vitro
[33, 97, 98]. Increase in the hydrophilicity of polyanhydride by increasing PEG
content in the polymer enhances the degradation rate even though it maintains
the surface-eroding property of polyanhydride [27]. Another important factor
which affects the polyanhydride degradation and erosion is geometry of the matrix.
It is very interesting to understand the macroscopic and microscopic degradation
properties of the polyanhydrides at the molecular level. It is reported that erosion
of matrices is strongly related to their geometry and rate of degradation for bigger
matrices was lower than smaller ones due to smaller surface area [27, 99-101]. For
example, during
in vitro
erosion of microspheres made of p(FAD-SA) 8:92, p(FAD-
SA) 25:75, and p(FAD-SA) 44:56 with average diameters below 100
m, SA was
released completely in 100 h, while the release time was in weeks from matrix
form of the polymer [102]. Some theoretical models have been proposed which
allowed description and prediction of the erosion behavior of polyanhydride matri-
ces [103]. Empirical models are based on the assumption of linear moving erosion
front [104-106]. Monte Carlo based models offered the advantages of degradation
modeling of the polymer as a random event that obeyed fi rst - order kinetics rather
than describing the degradation of individual bonds [100, 107-109].
μ
3.6
In Vivo
Degradation and Elimination of Polyanhydrides
Polyanhydrides were initially developed in matrix form as implantable drug carrier
systems. Thus, it is critical to understand the processes involved in degradation
and erosion in an
in vivo
environment and the differences between
in vitro
and
in vivo
degradation of polyanhydrides. Surface erosion of polyanhydrides depends
on the penetration of water into the matrix system to hydrolyze the anhydride
bonds. After hydrolysis, matrices degrade into degradation products of polyanhy-
drides and solubilize in the biological environment of the implantation site and
are eliminated. Polyanhydrides are composed of sparingly water-soluble diacid
monomers and thus elimination
via
solubilization in biological environment is a
slow process [110]. Aliphatic monomers such as SA will most likely participate in
the
β
-oxidation pathway yielding acetyl-coA which could be used in a typical bio-
