Microfluidic-assisted synthesized of oxaliplatin nanovehicles combined with curcumin polymeric micelles applied to chemoresistant colorectal cancer treatment

ELENA SANMARCO; JULIA GALLINO; DIEGO A. CHIAPPETTA; DAILENYS ESPINOSA MARTINEZ; FLORENCIA GIANNONI; MARTÍN CABALEIRO; RODRIGO LLOYD; MARIO GADÁN; MARCELA A. MORETTON; LUCÍA POLICASTRO

Mar del Plata

Otro; Reunión Anual de Sociedades de Biociencias (SAIC-SAFE-SAB-SAP); 2019

Resistance and metastatic recurrence are the main barriers for the effective treatment of cancer. Administration of antineoplastic drugs in 100nm-size nanovehicles (NV) optimizes the localization of drugs in tumor tissue. This occurs manly due to the enhancement permeably retention effect that reduce peripheral toxicity and increase the tumor local therapeutic effectiveness. Oxaliplatin (Oxp), is a high efficiency chemotherapeutic drug but with severe adverse effects, thus this encapsulation in NV could significantly improve the effect. Moreover, the combination of this chemotherapeutic drug with sensitizing molecules, such as curcumin (Cur), could yet increase the possibilities of therapy success. This molecule is highly hydrophobic, so its encapsulation in NV also could improve its delivery. However, NV conventional synthesis technologies are inefficient with variations in the batch-to-batch procedures, which make it difficult for a rapid translation to patients. In recent years, microfluidic technology-assisted nanomedicines synthesis, where fluid are subtly controlled, significantly improve these processes and allow reproducibility between different batches. The aim of this work is to administrate Oxp in liposomes and Cur in polymeric micelles performed by microfluidic technology in order to improve chemoresistant colorectal cancer treatment. We developed a micromixer chip for the encapsulation of Oxp in liposomes, obtaining optimal conditions in size and % of encapsulation of Oxp. Both compounds encapsulated, alone or in combination, were tested in Oxp resistant subcutaneous tumor in nude mice developed by our group and administrated by intravenous injection. The administration of the combination of encapsulated drugs produced a high effect in tumor growth with only one dose application. These results could have a high impact on the synthesis and the encapsulation of oncologic drugs in liposomes in the national and regional pharmaceutical industry.