Biomedical Engineering Reference
In-Depth Information
This technique increases entrapment effi ciency and removes any organic-water
interface from the manufacturing environment [19].
An alternative to using an organic solvent to mobilize the polymer phase uses
heat to melt the polymer. This has been used in the manufacture of Zoladex. The
temperatures required to mobilize PLGA can be above 100 °C (depending on the
composition and molecular weight) and so the technique is restricted for use with
drugs that are stable at these elevated temperatures. Recently, Ghalanbor
et al.
have
used hot-melt exclusion to load a protein, lysozyme, into PLGA. They demonstrated
loading of up to 20% w/w of protein in the polymer with full retention of the protein
enzymatic activity. The addition of PEG to the formulation eliminated the burst
release of drug and drug release was controlled over a 80- day period [20] .
The temperature of process of PLGA and many other polymers can be lowered
to below 37 ° C using CO
2
as a high-pressure processing medium. This technique
relies on CO
2
depressing the glass transition temperature of amorphous polymers
and lowering the viscosity of amorphous or crystalline polymer melts. High-
pressure and supercritical - CO
2
processing have been described for microparticles,
fi bers, and highly porous scaffolds containing numerous types of protein drug
[21 - 23] .
15.6
Examples of Biodegradable Polymer Drug Delivery Systems Under Development
15.6.1
Polyketals
Polyketal -based drug delivery systems are under development for applications in
which the acid degradation products from either poly(
- hydroxy acids) or polyanhy-
drides could cause detrimental side effects. Sy
et al.
have developed a poly(cyclohexane -
1,4-diylacetone dimethylene ketal)-based delivery systems that can be used in the
treatment of infl ammatory diseases such as cardiac dysfunction [24].
This polyketal degrades in the presence of acid and generated neutral products.
Sy
et al.
demonstrate that the encapsulation of a p38 inhibitor (SB239063) can
improve the treatment of myocardial infarction.
α
15.6.2
Synthetic Fibrin
The biodegradable polymers discussed so far in this chapter have all used a simple
water- or acid-triggered hydrolysis of a synthetic polymer backbone to lower their
molecular weight and convert from water-insoluble to water-soluble forms.
A recent trend in the design of new biodegradable polymers for drug delivery
has been to mimic enzymatic mechanisms of degradation used by our own bodies
to remove extracellular matrix (ECM) and fi brin clots during tissue turnover or
repair [25]. The need to employ this sophisticated method of controlling polymer
