Publications

Very recently, the controlled release of dopamine (DA), a neurotransmitter whose deficiency is associated with Parkinson's disease, has been postulated as a good alternative to the oral administration of levodopa (L-Dopa), a dopamine precursor, to combat the effects of said disease. However, this is still a very little explored field and there are very few carriers that are capable of releasing DA, a small and water-soluble molecule, in an efficient and controlled manner. In this work, we report a carrier based on a conductive hydrogel capable of loading DA and releasing it progressively and efficiently (100 % release) in a period of five days by applying small electrical stimuli (-0.4 V) daily for a short time (1 min). The hydrogel (CMC/PEDOT), which is electrically active, has been prepared from sodium carboxymethylcellulose and poly(3,4-ethylenedioxythiophene) microparticles, using citric acid as a cross-linking agent. Furthermore, the results have shown that when relatively hydrophobic small molecules, such as chloramphenicol, are loaded, the electrostimulated release is significantly less efficient, demonstrating the usefulness of CMC/PEDOT as a carrier for neurotransmitters.

JTD Keywords: Amines, Carboxymethyl cellulose, Carboxymethylcellulose, Conducting hydrogels, Conducting polymers, Controlled release, Crosslinking, Dopamine, Drug-delivery system, Electrostimulation, Hydrogels, Joining, Levodopa, Loading, Molecules, Neurophysiology, Neurotransmitter release, Neurotransmitters release, Oral administration, Parkinson's disease, Parkinsons-disease, Poly(3,4-ethylenedioxythiophene), Release, Sodium, Transport, Water-soluble molecule

Innovative insulin delivery systems contemplate combining multi-pharmacokinetic profiles for glycemic control. Two device configurations have been designed for the controlled release of insulin using the same chemical compounds. The first insulin delivery system, which displays a rapid release response that, in addition, is enhanced on a short time scale by electrical stimulation, consists on an insulin layer sandwiched between a conducting poly(3,4-ethylenedioxythiophene) (PEDOT) film and a poly-gamma-glutamic acid (gamma-PGA) hydrogel. The second system is constituted by gamma-PGA hydrogel loaded with insulin and PEDOT nanoparticles by in situ gelation. In this case, the insulin release, which only starts after the degradation of the hydrogel over time (i.e. on a long time scale), is slow and sustained. The combination of an on-demand and fast release profile with a sustained and slow profile, which act on different time scales, would result in a very efficient regulation of diabetes therapy in comparison to current systems, allowing to control both fast and sustained glycemic events. Considering that the two systems developed in this work are based on the same chemical components, future work will be focused on the combination of the two kinetic profiles by re-engineering a unique insulin release device using gamma-PGA, PEDOT and insulin.

JTD Keywords: Conducting polymer, Constant, Diabetes, Diabetes-mellitus, Drug-delivery, Electrodes, Electrostimulation, Glucose-responsive hydrogels, Hydrogel, Molecular dynamics, Molecular-dynamics, Nanogels, Nanoparticles, Poly(3,4-ethylenedioxythiophene), Risk

We describe a multi-tasking flexible system that is able to release a wide spectrum antibiotic (levofloxacin, LVX) under electrostimulation and act as a pH sensor for detecting bacterial infections. Combining anodic polymer-ization with plasma polymerization processes we engineered dual pH-and electro-responsive polymeric systems. Particularly, the manufactured devices consisted on a layer of poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHEDOT) loaded with the LVX antibiotic and coated with a plasma polymer layer of poly(acrylic acid) (PAA). The PHEDOT acted as conductive and electro-responsive agent, while the PAA provided pH responsiveness, changing from a compact globular conformation in acid environments to an expanded open coil conformation in alkaline environments. The assembly between the PHEDOT layer and the PAA coating affected the electro-chemical response of the former, becoming dependent on the pH detected by the latter. The conformational change experienced by the PAA layer as a function of the pH and the redox properties of PHEDOT were leveraged for the electrochemical detection of bacteria growth and for regulating the release of the LVX antibiotic, respectively. The effectiveness of the system as a stimulus-responsive antibiotic carrier and pH sensor was also investigated on strains of Escherichia coli and Streptococcus salivarius.

JTD Keywords: Conducting polymer, Delivery, Drug delivery, Electrostimulation, Levofloxacin, Ph sensor, Plasma, Poly(acrylic acid), Selective detection