title: Synthesis and characterization of micelles as carriers of non-steroidal anti-inflammatory drugs (NSAID) for application in breast cancer therapy.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDS) are emerging as a particularly valuable class of drugs due to their recently reported anti-tumoral activity in colorectal cancer. However, despite this tremendous potential, their bioavailability at the tumor microenvironment remains rather limited. To overcome this issue, in this work we synthesized biocompatible micellar nanocarriers composed of amphiphilic chitosan to deliver ibuprofen into breast cancer cells and evaluate its anti-tumor activity, while avoiding side-effects. Our results reveal that the formulations produced herein self-assembly into spherical micelles with suitable sizes for tumor accumulation (108-252 nm). Furthermore, by using a vortex-sonication method, ibuprofen was successfully encapsulated with high efficiency. Cell uptake studies show that ibuprofen-loaded micelles are readily internalized by tumor cells and deliver their cargo in the intracellular compartment as demonstrated by confocal microscopy images. This fact led to a remarkable reduction in cancer cell viability (<13%), at a relatively low drug dosage, illustrating the anti-tumoral activity of ibuprofen when delivered to breast cancer cells. These findings demonstrate the promising potential of chitosan micelles as carriers of cost-effective NSAIDS for application in breast cancer therapy.
authors.affiliation: CICS-UBI - Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal.
authors.forename: João G
authors.initials: JG
authors.lastname: Marques
authors.affiliation: CICS-UBI - Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal.
authors.forename: Vítor M
authors.initials: VM
authors.lastname: Gaspar
authors.affiliation: CICS-UBI - Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Costa
authors.affiliation: ITQB-UNL - Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da Republica, Estação Agronómica Nacional, 2780-157 Oeiras, Portugal.
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Paquete
authors.affiliation: CICS-UBI - Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal. Electronic address: icorreia@fcsaude.ubi.pt.
authors.forename: Ilídio J
authors.initials: IJ
authors.lastname: Correia
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008823:Micelles; D048271:Chitosan; D007052:Ibuprofen
keywords: Anti-proliferative activity; Breast cancer; Chitosan; Ibuprofen; Micelles; NSAIDs