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Received February 10, 1998; accepted March 12, 1998
KEY WORDS: genetic engineering; polymers; drug delivery.
The majority of the advanced drug delivery systems contain polymeric biomaterials as their central component. Whether commercially available or in the research stage, by and large biopolymers for drug delivery are synthesized using traditional synthetic methods which result in the production of polymers with heterogeneous molecular weights, and in the production of monomer sequences and compositions which can only be defined in terms of statistical distribution. Heterogeneity in molecular weight, composition, sequence, and stereochemistry influences the function of the biomaterial in drug delivery. For example water soluble polymeric drug carriers must have a narrow optimal molecular weight range, below which polymer molecules are eliminated too rapidly from the blood stream, and above which they are chronically retained in some organs such as liver, spleen, and bone marrow (1). The location and sequence of the recognition sites within the macromolecule affect the biorecognition of the polymer by the biological enzymes or receptors, and consequently influence drug targeting and release (2). Stereochemistry of copolymers of lactic-glycolic acid influences the rate of degradation and drug release from these systems (3). Therefore a higher degree of control over the molecular weight, composition, sequence, and stereochemistry of the bioploymer may have a profound effect on the biological fate and the function of the biomaterial as the drug carrier.
The purpose of this commentary is to introduce pharmaceutical scientists to an emerging technology that promises to provide unique potential to the field of drug delivery. A list of references is provided with more detailed information for critical review. This new technology renders a higher degree of control over the macromolecular structure of synthetically designed proteins using genetic engineering techniques. Methods for the successful design and biological synthesis of high molecular weight structural protein polymers were first developed in 1986 (4), and have been shown to be generally applica-ble to the synthesis of a variety of proteins consisting of repeating blocks of amino acid sequences (5-7). Precise control over the biomaterial structure through sequence specification is the key advantage of the new synthetic methodology. As an example, a biologically synthesized polymer comprising 36 repeats of the octapeptide sequence-(AlaGly)3GluGly-was designed to adopt folded-chain lamellar architecture in the...