Starch chemical modifications applied to drug delivery systems: From fundamentals to FDA-approved raw materials.

Starch derivatives are versatile compounds that are widely used in the pharmaceutical industry. This article reviews the advances in the research on hydrophilic and hydrophobic starch derivatives used to develop drug delivery systems over the last ten years, specifically microparticles, nanoparticles, nanocrystals, hydrogels, and scaffolds using these materials. The fundamentals of drug delivery systems, regulatory aspects, and chemical modifications are also discussed, along with the synthesis of starch derivatives via oxidation, etherification, acid hydrolysis, esterification, and cross-linking. The chemical modification of starch as a means to overcome the challenges in obtaining solid dosage forms is also reviewed. In particular, dialdehyde starches are potential derivatives for direct drug attachment; carboxymethyl starches are used for drug encapsulation and release, giving rise to pH-sensitive devices through electrostatic interactions; and starch nanocrystals have high potential as hydrogel fillers to improve mechanical properties and control drug release through hydrophilic interactions. Starch esterification with alginate and acidic drugs could be very useful for site-specific, controlled release. Starch cross-linking with other biopolymers such as xanthan gum is promising for obtaining novel polyelectrolyte hydrogels with improved functional properties. Surface modification of starch nanoparticles by cross-linking and esterification reactions is a potential approach to obtain novel, smart solid dosages.