Controlled release from recombinant polymers

Abstract

Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed.

Keywords: Controlled release; Elastin-like Polypeptides (ELP); Recombinant Cationic Polymers (RCP); Recombinant polymers; Silk-elastinlike Protein Polymers (SELP); Silk-like Polypeptides (SLP).

Figure 1

Generalized schematic of recombinant polymer synthesis

Figure 2

Amino acid sequence of selected silk-elastinlike protein polymers. Note: Single letter amino acid code is used, head and tail sequences omitted for clarity.

Figure 3

β-galactosidase expression in xenograft tumors injected with adenovirus released from SELP47K (47K), SELP415K (415K), and SELP815K (815K) assayed at weeks 1, 2, and 3. Reproduced with permission from [104].

Figure 4

Protein loss (top) and particle release (bottom) as a result of digestion of SELP815K (left) and SELP815K-MMPRS (right) gels by matrix metalloproteinase enzymes. Reproduced with permission from [115]