Materials and biological aspects of synthetic polymers in controlled drug release systems: problems and challenges.

The physico-chemical and biological aspects of polymeric materials represent vital areas in the reliable, safe, and efficacious functioning of controlled drug-delivery devices. In the case of implantable systems, potential biological problems include incompatibility of the polymers and their degradation products with the physiological environment, adverse metabolic consequences of the degradation products, and occlusion of the drug conduits (catheters) with thrombi and/or drugs, (i.e., insulin aggregates). In the case of transcutaneous drug delivery systems, proper consideration must be given to avoid skin irritation and allergic responses as well as other toxic effects. With biodegradable systems that may follow simple hydrolysis and/or enzyme-catalyzed degradation of labile chemical side-chains that hold the drug molecule and/or the main polymer chain, increased attention must be given not only to the short-term but also the long-term metabolic consequences of the degradation products. Although the term "biodegradation" is often used for in vitro situations it should be reserved only for in vivo circumstances as, at the present time, no in vitro experiments can completely simulate the in vivo environment. The misuse of this term may lead to premature predictions as to the performance of a device in vivo, a situation that ought to be avoided. Appropriate attention must also be given to the effect of drugs on polymers as drug/polymer interactions may influence the stability of both the polymers and drugs and may result in altered therapeutic performance. Standards are needed to clearly differentiate between controlled drug delivery systems and older "sustained" and "time-release" preparations.