Polyanhydrides implantable systems

Particulate systems (e.g., collagen, lactic or glycolic acids, polyanhydride or polyethylene vinyl coacetate) have several potential advantages for the therapeutic delivery of DNA (or of drugs), such as DNA encapsulation within the polymer can protect DNA degradation until release injection or implantation of the polymer into the... 

Historically, polyanhydrides were synthesized for engineering materials. Because of their hydrolytical instability, these polyanhydrides have never been commercialized for engineering purposes. This instability has a beneficial aspect in drug delivery systems since the implant incorporated with an active drug does not need to be retrieved. The anhydride has a labile bond in the main chain of the polymer. This labile bond then breaks down into two carboxylic acid groups. 

Biocompatible ortho aromatic polyanhydrides, (IV), prepared by Uhrich [5] were used in drug delivery systems and as scaffolding implants for tissue reconstruction. 

The biocompatibility of implantable polyanhydride disks was studied in the brain of rats, rabbits, monkeys, and eventually in human clinical trials. Wafers of poly(CPP SA) and poly (FAD SA) were implanted in the frontal lobes of rats, rabbits, and monkeys. In all these studies, the animals receiving the implants showed no behavioral changes or neurological deficits, indicating that the polymers were not invoking a systemic or local toxicity. To determine how the body metabolized the poly(CPP SA), radio-labeled copolymers were implanted in the brains of rats. Seven days after the implantation, 40% of the " C SA-labeled polymer had been excreted as CO2, 10% was excreted along with the urine, 2% with the feces, and 10% still in the implanted device. In the same period only 4% of the " C CPP-labeled polymer was excreted along with the urine and feces. 

A separate polyanhydride system has also been investigated for the treatment of osteomyelitis, a bone infection typically caused by bacteria. ° Copolymer implants (50 50 FAD SA) containing gentamicin were tested in the backs of rats, in the infected tarso-crural joints of horses, and in humans with infected prosthetic hips or knees. In all the cases, the local delivery of gentamicin was successful and the systemic exposure to the drug was avoided. 

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