Starch and Its Use for Drug Delivery

Starch is one of the most abundant renewable biopolymers on Earth and is nonallergenic, GRAS (generally recognized as safe), and cheap [132]. It is found in peas, corn, rice, wheat, potato, and beans [133]. Starch granules vary in size, shape, particle size distribution, and in the amylose–amylopectin ratio depending on the botanical origin and maturity [134]. The high encapsulation efficiency was reached when the amylose:amylopectin ratio was 25:75 [135]. Starch granules are composed of amylose and amylopectin, free fatty acids and lysophopholipids, proteins, phosphate esters, and water [136]. Amylose is the linear fraction and is composed of glucopyranose units linked by α-(1,4)-glycosidic linkages, while amylopectin is a highly branched polymer with short α-(1,4)-glycosidic chains linked by α-(1,6)-glycosidic branching points [137]. Although amylopectin has a high viscosity and is a good thickening agent, it produces very weak gels with poor mechanical properties [138]. Starch is a biopolymer available in the form of powders, hydrogels, films, and sponges [139]. Due to its low cost, physicochemical features, biodegradability, and biocompatibility, native and modified starch has been widely used in the food, chemical, pharmaceutical, and environmental industries [140].

In the pharmaceutical and medical industries, starch has been used as a pharmaceutical excipient, a tablet super disintegrant (immediate release tablet formulations), and a

controlled/sustained-release polymer or as plasma volume expander, useful for patients suffering from trauma, heavy blood loss, or in cancer treatment [141]. Research has focused on the ability of native starch to be dissolved by pancreatic enzymes after oral ingestion, followed by absorption from the small intestine into the systemic circulation. There is also a resistant part of starch that is not digested in the small intestine and is fermented by colonic bacteria. When used as an encapsulant for drugs, it is combined with other biopolymers precisely to limit or attenuate enzymatic degradation in the stomach, thus facilitating the absorption of an adequate amount of the therapeutic agent [142]. In pharmacotherapy, the main objective of such a system is to provide controlled drug release and prevent fluctuations of active substances in the blood in order to maintain drug plasma concentration within the optimal range, in accordance with therapeutic recommendations.

Starch with high crystallinity levels has been explored as an encapsulation matrix. In order to be used successfully in drug delivery and other industries, starch can be modified so that the physicomechanical properties are adjusted to maximize its use. Starch can be modified by chemical, physical, enzymatic, and genetic processes. Of these, chemical process is used most frequently due to its non-disintegrating nature and potential increase in the functionality of the modified starch. The applications of starch as an encapsulating agent of active substances are presented in Table 4.


**Table 4.** Applications of starch for drug delivery.


Most starch-based drug delivery systems have been developed with starches extracted from potato, maize, corn, cassava, and wheat [118]. As shown in Table 4, starch is a viable source of biopolymer, used as an encapsulating agent for controlled drug delivery systems. In its unmodified form, starch is not as effective as a drug delivery system due to poor mechanical properties, such as low shear stress resistance or high retrogradation and syneresis, thermal decomposition, reduced processability, and solubility in common organic solvents [156]. However, after modification, starch can be used successfully for this purpose. For example, modifying starch in order to obtain resistant starch has led to its use for improving the gut microbiota population with a role in modulating signaling pathways associated with anti-inflammation, anti-diabetes, and anti-obesity [157]. Resistant starch, due to its high amylose content and low amylopectin, has been recognized as a healthy food for humans and animals. It can be considered prebiotic and may reach the colon due to its resistance to digestion by pancreatic enzymes in the small intestine [158]. Therefore, encapsulation has been suggested as the best approach to improve prebiotic– probiotic symbiosis.
