DUAL PH-ENZYMATIC RESPONSIVE CROSSLINKED CASEIN MICELLES AS SMART CARRIERS OF HYDROPHOBIC DRUGS IN CONTROLLED DELIVERY SYSTEMS FOR CANCER THERAPY

JULIO C. CUGGINO; ROQUE MINARI; MARCELO CALDERÓN; GREGOR NAGEL; CECILIA I. ALVAREZ IGARZABAL; MATIAS L. PICCHIO; STEFANIE WEDEPOHL; LUIS M. GUGLIOTTA

Bahia Blanca

Workshop; III workshop de polimeros biodegradables y biocompatibles; 2018

Planta Piloto de Ingeniería Química (PLAPIQUI), instituto de investigaciones dependiente de la Universidad Nacional del Sur (UNS) y del Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)

New types of biodegradable nanocarriers were prepared from casein micelles using glyceraldehyde as crosslinker. We found that highly crosslinked casein micelles (CCM) could be easily degraded in the presence of proteases and pH 5 (intracellular conditions) but they maintain their structure at pH 7.4 (plasma conditions). Nile red (NR) was chosen as a model hydrophobic dye inspired by the natural role of casein as lipophilic-nutrient delivery nanovehicles. The release of NR was activated by enzymatic and pH degradation of the nanocarries in intracellular conditions. The cumulative release profile of the NR-loaded micelles showed a low level of dye release at pH 7.4, and was significantly accelerated at pH 5.0 in presence of trypsin. The nanovehicles prepared possess excellent biocompatibility and biodegradability, stability in physiological conditions and rapid drug release in response to the intracellular level of pH and enzymatic degradation. These properties endow the CCM as a promising candidate for triggered drug delivery.