Biomedical Engineering Reference
In-Depth Information
otherapeutic agents through BBB [141]. Various polyanhydrides and drug combi-
nations have been used to obtain the optimum release profi le and treat the brain
tumor or glioma. Gliadel wafer is one of the most successful delivery systems
using polyanhydride and is commercially available. Gliadel has been approved in
1996 by the US-FDA for the use as an adjunct to surgery to prolong survival in
patients with recurrent Glioblastoma multiforme for whom surgical resection is
indicated [142]. An additional approval from US-FDA in February 2003 has been
granted for the use of Gliadel in patients with newly diagnosed high-grade malig-
nant gliomas, as an adjunct to surgery and radiation. A study has been performed
by Frazier
et al.
[143] to fi nd the effi cacy of local delivery of minocycline and sys-
temic BCNU on intracranial glioma. Minocycline, an antiangiogenic agent, was
incorporated in P(CPP:SA) at a ratio of 50:50 by weight and found that the combi-
nation of intracranial minocycline and systemic BCNU extended median survival
by 82% compared to BCNU alone (
p
<
0.0001) and 200% compared to no treat-
ment (
p
0.004). Polyanhydride matrix has been used to deliver heparin and cor-
tisone acetate as antineoplastic agent. They have reported the inhibition of growth
of 9L glioma and found out that in the presence of heparin and cortisone, and of
cortisone alone, there was a 4.5- and 2.3-fold reduction, respectively, in the growth
of 9L glioma [144]. A potential paclitaxel (taxol) formulation in polymeric disk of
P(CPP:SA, 20:80) with 20-40% of taxol loading, and maintained concentration of
75 - 125 ng taxol/mg brain tissue, within 1 - 3 mm radius of the disk [145] . Another
polyanhydride system for delivery of taxol has been formulated using P(FAD:SA,
50:50) but, due to the hydrophobic nature of the FAD, the release rate was very
slow and therapeutic concentration could not be achieved [146]. 4-HC, a hydrophilic
derivative of cyclophosphamide, with and without
t
- buthionine sulphoxine (inhib-
iting glutathione synthesis, which catalyzes inactivators of alkylating agents), was
incorporated in P(FAD:SA) and found to be effective in rat intracranial 9L gliosar-
coma and F98 glioma model [147-149]. Fluorodeoxyuridine, an antimetabolite, has
also been optimally released from P(FAD-SA) polymer
in vitro
and
in vivo
[150] .
Adriamycin incorporated in P(CPP:SA) has shown improved median survival in
rat intracranial 9L glioma model [151]. Fifty percent 5-iodo-2
<
- deoxyuridine con-
taining P(CPP:SA, 20:80) have been used successfully for radiosensitization of
experimental human malignant gliomas [152] Methotrexate-dextran conjugate (to
improve stability and inhibit degradation of MTX) when incorporated in P(FAD:SA)
offered signifi cant improvement over controls in rat intracranial 9L glioma [151].
Recently, antineoplastic RANse encapsulated in P(RA-SA) implants showed prom-
ising effi cacy against 9L glioma, while evading neurotoxicity in the cerebellum.
The controlled release of Amphibinases forms the potential for a new therapy
against brain tumors [153]. Carboplatin and camptothesin are the other anticancer
molecules which have shown promising results when incorporated in the
P(CPP:SA) [154, 155]. Further, various chemotherapeutic drugs such as ciplatin,
methotreaxte, etc., have been delivered using fatty acid-based polyanhydride in
squamous cell carcinoma of head and neck. [16, 35, 156, 157].
Osteomyelitis is another disease condition where polyanhydride implant (Sep-
tacin) has been found successful in effi cacious delivery of gentamicin clinically
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