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.
Liver S9 (LS9) is a nearly complete collection of all hepatic drug-metabolizing enzymes. It is a low-cost model for predicting drug metabolic activity. This study aimed to identify the suitability of using LS9 of different animal sources in drug metabolism profiling with respect to the possible translation of the in vitro outcomes to clinical studies. The in vitro hepatic metabolism of curcumin diethyl disuccinate (CDD) in LS9 of rats, dogs, monkeys, and humans was evaluated. The identity of CDD metabolites and the metabolism kinetic parameters, including degradation rate constant, in vitro/in vivo intrinsic clearance, and half-life, were determined. CDD was rapidly metabolized into monoethylsuccinyl curcumin and curcumin in LS9 of all tested species mainly by carboxylesterases (CESs), including CES1 and CES2, and butyrylcholinesterase. The in vitro intrinsic clearance of CDD was in the order of human > dog > monkey > rat, whereas that of monoethylsuccinyl curcumin in the order of dog > monkey > human > rat; this parameter was not correlated with their respective in vivo clearance, which followed the order of dog > monkey > rat > human. Therefore, in vitro drug metabolism data inferred from LS9 of nonhuman origin, especially from monkeys and dogs, cannot be used as preclinical data for human trials, as humans have a smaller liver-to-body weight ratio than monkeys, dogs, and rats. The in vivo drug metabolism is dictated by the anatomical factors of the test subject.