Gliadel implant

Gliadel - a controlled-delivery polymer wafer is the combination of a copolyanhydride matrix consisting of CPP and sebacic acid (20/80 mol. ratio) in which an anticancer agent is physically admixed. Clinical investigations of Gliadel implants in rabbit brains have shown limited toxicity, initial activity and fast excretion of decomposition products as free acids (J4). 

The encapsulation and release of l,3-bis(2-chloroethyl)nitrosourea (BCNU) in P(CPP-SA) 20 80 wafers was the first implantable controlled release device based on polyanhydrides that was FDA-approved and marketed (Gliadel ) (Chasin et al., 1988). BCNU was encapsulated by two techniques, trituration and co-dissolution, resulting in different release profiles (Chasin et al., 1990, 1991). The triturated samples released faster than those prepared by co-dissolution, presumably due to more homogeneous loading in the samples prepared by co-dissolution. 

Gliadel is a biodegradable polyanhydride implant composed of poly[bis(p-carboxyphenoxy) propane sebacic acid] in a 20 80 monomer ratio, for the delivery of carmustine. The implant is indicated in the treatment of recurrent glioblastoma multiforme (GBM) which is the most common and fatal type of brain cancer. 

Brain tumors myeloma NHL HD BMT preparative regimens melanoma also available in wafer form for implantation into brain tumor cavities after resection (Gliadel)... 

Implantable delivery systems offer a number of advantages over more traditional delivery routes, particularly for biological macromolecules (including peptides, proteins, and oligonucleotides). Some specific delivery mechanisms to date include polymer depots (e.g., Gliadel Wafer, prolifeprosan 20 with carmustine implant) and osmotic pumps (e.g., Viadur leuprolide acetate implant). 

Apart from these polymers, some polyanhydrides have undergone active clinical development. Polyanhydrides involving sebacic acid (hydrophilic component) and carboxyphenoxypropane (hydrophobic component) have been used to develop a matrix for Gliadel , a commercial product for the sustained release of carmustine, an anti-cancer drug used in the treatment of brain tumours. Other anhydrides have also been investigated, such as poly-(erucic acid dimer sebacic acid 50 50) copolymers for the development of implants for the antibiotic treatment of osteomyelitis. 

MAJOR APPLICATIONS Biodegradable polymer for controlled drug delivery in a form of implant or injectable microspheres (e.g., Gliadel -BCNU-loaded wafer for the treatment of brain tumors). 

Dang, W., Daviau, T., Brem, H., 1996. Morphological characterization of polyanhydride biodegradahle implant Gliadel during in vitro and in vivo erosion using scanning electron microscopy. Pharmaceutical Research 13, 683—691. 

Dang, W., Daviau, T. and Nowotnik, D. (1996) In vitro erosion kinetics of implantable polyanhydride Gliadel . Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 23, 731-2. 

Gliadel = polyanhydride brain tumor implant containing BCNU... 

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