Aplicaciones biomédicas de matrices poliméricas fototérmicas

Abstract

Drug delivery systems are tools designed to administer therapeutic agents in a controlled manner to specific organs or tissues in need of therapy. In this work, we have developed photothermal hydrogels as platforms for controlled delivery of therapeutic agents. To this aim, we have included metallic nanoparticles having photothermal activity at near-infrared (NIR) wavelengths in polymeric matrices. Incorporation of thermosensitive liposomes loaded with an antitumoral drug within photothermal fibrin matrix resulted in NIR-responsive lipogels that released their liposomal cargo after NIR irradiation. Released drug maintained their bioactivity as tested in cultures of human cervical carcinoma cells. Levels of drug released from the constructs were dependent on the type and concentration of NIR nanotransducers loaded in the lipogel, the intensity of deposited electromagnetic energy and the irradiation regime. The developed drug delivery platform was improved by the incorporation of cholesterol in thermosensitive liposomes formulation, which lessened leakiness of the liposomal cargo at physiological temperature and increased drug release after thermal treatment. Photothermal matrices technology was also used to prepare NIR responsive scaffolds that are able to control transgenic expression, allowing to achieve spatiotemporal control over the bioavailability of therapeutic gene products. Photothermal nanoparticles were included within polymeric fibrin matrices, elastin like recombinamers (ELR) and cryogels of hydroxyethyl methacrylate and acrylic acid copolymers. These matrices were biocompatible and transduced efficiently NIR energy into heat to activate transgene expression in cells harboring a gene switch triggered by heat and dependent on a low molecular weight ligand. Multipotent stem cells incorporated within fibrin hydrogels that include photothermal nanoparticles based in copper sulfide (CuSNP) increased metabolic activity, survival rate and fibrinolytic activity and displayed changes in their transcriptome related to angiogenic response. Endothelial cells entrapped within these matrices formed pseudocapillary structures and remodeled protein matrix. Long term implantation of CuSNP fibrin matrices induced an angiogenic response that facilitates its integration into the host tissue while implantation of photothermic ELR matrix and cryogels was characterized by low inflammation response and limited biomaterial degradation.