Polymeric carriers: preclinical safety and the regulatory implications for design and development of polymer therapeutics.

Since the early 1990s polymer-protein conjugates (included PEGylated enzymes and cytokines), polymeric drugs and polymeric sequestrants have been entering the market as innovative polymer-based therapeutics. Initially these products were most frequently developed as novel anticancer agents; indeed they can be considered first generation "nanomedicines". More recently, a much broader range of life-threatening and debilitating diseases (e.g. viral infections, arthritis, multiple sclerosis and hormone abnormalities) have been targeted via intravenous (i.v.), subcutaneous (s.c.) or oral routes of administration. Given the increasing novelty of polymeric materials proposed for development as second-generation polymer therapeutics (with increasing complexity of conjugate composition), and the growing debate as to the safety of nanomedicines per se, the need for evolution of an appropriate regulatory framework is at the forefront of the scientific discussion. The adequacy of the current tests and models used to define safety are also constantly being reviewed. Here we describe the current status and future challenges in relation to these issues.