Biomedical Engineering Reference
In-Depth Information
acid component (see Section 15.3.1) as it has a profound effect on the physical and
biological behavior of these polymers.
The polymers in this family have been components of biodegradable sutures
and orthopedic implants for many years providing a long history of use in the
human body. PLGA systems possess many attributes that make them suitable for
drug delivery applications in which a slow release of a drug within a device is
required [8]. Principle attributes are given below:
1 )
Ability to control the kinetics of polymer degradation
For detailed explanation of control, see review by Anderson and Shive [6] and
papers of Vert
et al.
[7-13], for example, A summary of key features of methods
of control are discussed below.
2 )
Numerous routes to fabrication
Described in Section 15.6.4.
3 )
Mechanical properties
Suffi cient compressive and tensile strength for use in applications in which
the delivery system will be under compression or tension during function.
For example, the polymer class is used in orthopedic implants.
4 )
Widely available at medical grade
Synthesized to high purity and following good manufacturing practice by a
number of companies across the world.
The history of use of PLGA polymers provides a number of important lessons for
the development of new classes of polymers. Despite the simplicity of the polymer
chemistry of PLGA polymers, the broad use of these polymers in humans and
animal models has exposed signifi cant complexity in the behavior of these poly-
mers
in vivo
. Section 15.3.1 highlights some of the complexity and draws heavily
on the excellent review of Anderson and Shive [8].
15.3.1
Controlling Degradation Rate
There are two distinct steps in the breakdown and removal of a biodegradable
polymer; degradation and erosion. Degradation is the chemical breakage of bone
along the polymer backbone that results in a decrease in polymer molecular
weight. Erosion is the loss of mass from the delivery system due to the dissolution
of the products of degradation.
The kinetics of degradation and erosion are determined by chemical and physi-
cal properties of the drug delivery system. A major attraction of the poly(
- hydroxy
acids) is the ability to use the ratio of lactic acid to glycolic acid in the polymer
chain to control both sets of kinetics. The methyl group on the lactic acid monomer
retards hydrolysis of the neighboring ester group compared with the glycolic acid
α
