Reinvention of starch for oral drug delivery system design

Starch is a polysaccharide with varying amylose-to-amylopectin ratios as a function of its biological sources. It is characterized by low shear stress resistance, poor aqueous/organic solubility and gastrointestinal digestibility which limit its ease of processing and functionality display as an oral drug delivery vehicle. Modulation of starch composition through genetic engineering primarily alters amylose-to-amylopectin ratio. Greater molecular properties changes require chemical and enzymatic modifications of starch. Acetylation reduces water solubility and enzymatic digestibility of starch. Carboxymethylation turns starch acid-insoluble and aggregative at low pHs. The summative effects are sustaining drug release in the upper gut. Acid-insoluble carboxymethylated starch can be aminated to provide an ionic character essential for hydrogel formation which further reduces its drug release. Ionic starch can coacervate with oppositely charged starch, non-starch polyelectrolyte or drug into insoluble, controlled-release complexes. Enzymatically debranched and resistant starch has a small molecular size which confers chain aggregation into a helical hydrogel network that traps the drug molecules, protecting them from biodegradation. The modified starch has been used to modulate the intestinal/colon-specific or controlled systemic delivery of oral small molecule drugs and macromolecular therapeutics. This review highlights synthesis aspects of starch and starch derivatives, and their outcomes and challenges of applications in oral drug delivery.