Biomedical Engineering Reference
In-Depth Information
be prepared by solvent casting the polymer solution containing the drug onto
Tefl on-coated dish [124]. Microsphere-based delivery systems can be formulated
by the common techniques including solvent removal, hot-melt encapsulation,
and spray drying [125-132]. Some recent studies report nanoparticles formulation
with polyanhydride and thus increasing the spectrum of application for polyanhy-
drides [133-137]. However, it is essential that all processes be performed under
anhydrous conditions to minimize hydrolysis of the polymer.
3.9
Production and World Market
Polyanhydrides are not commercially available. One polyanhydride composition,
poly(CPP-SA) (20:80), is manufactured at Guilford Pharmaceuticals in Baltimore
on a kilogram scale, as part of the Gliadel implant for the treatment of brain
tumors. Poly(dimer eurecic acid-
co
-sebacic acid) was developed for large- scale
production by Abbott Lab (Chicago) for the fabrication of the Septacin implant for
prevention of bone infections. The Septacin product was manufactured by injec-
tion molding of the polymer-drug composition. The development of this product
was stopped for marketing reasons. Samples of polyanhydrides may be obtained
by a request from the corresponding author.
3.10
Biomedical Applications
Polyanhydrides themselves and there hetero-copolymers with -amide, -ester, etc.,
have been used for diverse biomedical applications. Polyanhydrides fi nd major
application in controlled drug delivery. Delivery of chemotherapeutic drugs in
cancer is the major area of research for localized delivery using polyanhydrides.
There are about 60% of cancer patients with localized disease and it has been
estimated that around 32% of localized cancer patients face recurrence, following
initial treatment. Most of the anticancer drugs which are in clinical use do not
have specifi c effects on invasiveness or the tendency to metastasize but they are
only antiproliferative [138], and therefore, these drugs affect all the rapidly dividing
cells including normal tissues and show dose-limiting toxic effects.
First - order targeting is increased delivery of drug to the body compartment,
while second-order targeting is increased drug delivery to tumor cells; and intracel-
lular delivery is third- order targeting [138] . First - and second - order targeting is
achieved by local delivery using polyanhydrides through systems like implant,
surgical paste, microspheres, etc. Drug delivery in brain tumor (Glioblastoma
multiforme) is important aspect as many of the anticancer drugs are large, ioni-
cally charged or hydrophilic, and not able to cross the BBB; intolerably high sys-
temic drug levels are required to achieve the therapeutic doses within CNS [139,
140]. Localized delivery resolves the problem associated with permeability of chem-
