Polyanhydrides toxicity

Polyanhydrides have been chosen for the preparation of microspheres because of their degradation by surface erosion into apparently non-toxic small molecules.f The mixture of polymer and active ingredient is suspended in a miscible solvent, heated 5°C above the melting point of the polymer and stirred continuously. The emulsion is stabilized by cooling below the melting point until the droplets solidify. 

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. 

Polyanhydrides are useful bioabsorbable materials for controlled drug delivery. They are hydrolytically unstable and hydrolyze to diacid monomers in contact with body fluids. Since their introduction to the field of controlled drug delivery, about 10 years ago, extensive research has been conducted to study their chemistry as well as their toxicity and medical applications. Several review articles have been published on polyanhydrides and the focus has been on controlled drug delivery applications [1, 2]. 

A major part of this chapter will review recent developments in the chemistry and properties of polyanhydrides, which includes new synthetic methods, new polymeric structures, and in depth characterization of polyanhydrides. The degradation and drug release properties and applications that were not reviewed previously are included. A review article by the same authors concentrating on polyanhydride applications and toxicity is in preparation [6]. 

A comprehensive evaluation of their toxicity showed that, in general, the polyanhydrides possess excellent in vivo biocompatibility. Their employment in load-bearing orthopedic applications, however, is restricted owing to inadequate mechanical properties. Polyanhydrides-based devices for bone repair are limited to drug-release systems, as in the ease of poly(sebaeie anhydride) (PSA) and poly-D,L-lactide (PLA), for the treatment of ehronie osteomyelitis and in the prophylaxis of bone infeetion." ... 

Katti DS, Lakshmi S, Langer R (2002) Toxicity, biodegradation and elimination of polyanhydrides. Adv Drug Deliv Rev 54 933-961... 

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