Biomedical Engineering Reference
In-Depth Information
A further complication in predicting and understanding the kinetics of degrada-
tion of this family of polymers is the effect of device size and architecture. Coun-
terintuitively large device made from PLGA degrade more rapidly than
microparticles in certain circumstances [15]. In addition, an important clue in the
mechanism of accelerated degradation of large devices is the fi nding that large
rods of PLGA often become hollow during degradation. These phenomena can be
explained by the process of autocatalysis in which the acidic degradation products
of PLGA hydrolysis accelerate local degradation. This localized catalysis is greatest
within large devices due to the slow escape of the acid species. Hence, heterogene-
ous degradation kinetics occur across devices that have a diameter or width
>
300
μ
m.
15.4
Polyanhydrides
The second class of biodegradable polymers approved for use in humans in a drug
delivery application are the polyanhydrides. The product Gliadel has been used for
the treatment of brain tumors (see Section 15.2). A comprehensive review has
been published by Katti
et al.
[16] .
The motivation for using polyanhydrides over poly(
-hydroxy acids) is the need
to restrict polymer erosion to the surface of the devise. As described in Section
15.3, the PLGA systems erode through a bulk mechanism for small particles and
an autocatalytic hollowing mechanism for large rods. These mechanisms result
in the encapsulated drug contacting with water for extended periods before the
drug is released. Therefore, drugs that are sensitive to hydrolysis or other water-
mediated instabilities could lose activity over time in the PLGA devices. A surface-
eroding device would keep the drug dry prior to release. A further advantage of
a surface-eroding system is the ability to control drug release kinetics via changes
in surface area of the delivery system. For PLGA systems, the relationship
between polymer degradation, drug release, and surface area is very diffi cult to
predict (because bulk effects dominate and can be erratic due to physical breakup
of the delivery system).
The Gliadel system is formed from a copolymer of the monomers
bis(carboxyphenoxy)propane (CPP) and sebacic acid (SA). The structures of these
monomers and the generic anhydride structure are shown below. Although no
other polyanhydrides have been used in approved pharmaceutical products to date,
the fi eld of polyanhydride chemistry is active, and promising new structures are
under investigation.
α
General PAA structure:
O
O
*
R
O
*
n
