Hierarchical structured materials for controlled oral drug delivery

Abstract

We discuss here several strategies to answer key challenges related to the delivery of fragile hydrophilic molecules in the body from nanoparticles. The questions associated with these questions are: How to encapsulate a hydrophilic fragile drug while preserving its function and integrity? How to ensure that the nanoparticles encapsulating the fragile payload are not aggregated when dispersed in aqueous media? And finally, is it possible to fabricate a material that would allow for the delivery of a fragile drug in the blood when the drug is taken orally? In this work, we first discuss the state of the art related to the relevant topics. We summarized the currently available strategies to preserve fragile molecules. Moreover, we give also an insight into the techniques used to recover nanoparticles produced in inverse emulsions. We report a new strategy for the synthesis of pH-responsive nanocarriers for the controlled release of peptides. The main drawbacks of the common polyelectrolyte complexation method were overcome by confining the complexation reaction in nanodroplets of inverse miniemulsion and by subsequent interfacial crosslinking. The resulting nanocarriers released encapsulated peptide drug in response to changes in pH values. Afterward, the pH-responsive nanocarriers were further loaded into nanofibers constructed with a pH-responsive polymer, allowing for a stepwise release of payloads at sequential events of pH change. The hierarchically structured nanoparticle-in-nanofiber systems showed potential in complicated drug delivery tasks such as oral delivery of peptide drugs. Finally, the “cushion” method, a new method for the recovery of hydrophilic NPs was introduced. The fast, mild, and efficient “cushion” method enabled the re-dispersion of a CS-based nanocarrier in water without additional surfactant. We believe that the “cushion” method is also suitable for other water compatible nanocarriers.