Crosslinked casein-based micelles as a dually responsive drug delivery system

PICCHIO, MATIAS LUIS; CUGGINO, JULIO CESAR; NAGEL, GREGOR; WEDEPOHL, STEFANIE; MINARI, ROQUE J; ALVAREZ IGARZABAL, CECILIA INES; GUGLIOTTA, LUIS MARCELINO; CALDERON, MARCELO

Polymer Chemistry

Royal Society of Chemistry

Año: 2018

1759-9954

New types of biodegradable nanocarriers for drug delivery were prepared using casein(CAS) micelles as particle templates and glyceraldehyde (GAL) as a crosslinking agent.We found that highly crosslinked casein micelles (CCM) maintained their structural integrity at pH 7.4 (plasma conditions) but were easily degraded in the presence of proteases at pH 5 (lysosomal conditions). Nile red (NR) was chosen as a hydrophobic model drug inspired by the natural role of casein as lipophilic nutrient nanotransporter.The cumulative release of the NR-loaded micelles showed marginal dye leakage at pH 7.4 but was significantly accelerated by protease and pH−mediated degradation of the nanocarriers in a dual-responsive fashion. The prepared nanocarriers possess many favorable features for drug delivery: excellent biocompatibility and biodegradability,high stability in physiological conditions, remarkable capacity for the encapsulation of hydrophobic drugs, minimal drug leakage under extracellular conditions, and rapid drugrelease in response to the endo-lysosomal levels of pH and proteases. In this regard, the prepared CCM represent a promising candidate for the delivery and triggered release of anti-cancer drugs in lysosomal environments.