Publications

Bacterial infections pose a significant global health challenge aggravated by the rise of antimicrobial resistance (AMR). Among the obstacles preventing effective treatment are biological barriers (BBs) within the body such as the mucus layer. These BBs trap antimicrobials, necessitating higher doses and ultimately accelerating AMR. Addressing this issue requires innovative therapeutic strategies capable of bypassing BBs to deliver drugs more effectively. Here, we present nanomotors (NMs) based on hyaluronic acid (HA)- and urease-nanogels (NGs) as a solution to navigate effectively in viscous media by catalyzing the decomposition of urea into ammonium and carbon dioxide. These HA-based nanomotors (HA-NMs) were loaded with chloramphenicol (CHL) antibiotic and demonstrated superior antimicrobial activity against Escherichia coli(E. coli) compared to mesoporous silica NMs (MSNP-NMs), a reference in the field of NMs. Moreover, using an in vitro transwell model we evaluated the ability of HA-NMs to penetrate mucin barriers, effectively reducing E. coli proliferation, whereas the free antibiotic did not reduce bacteria proliferation. The optical density reduction at 24 h was over ten times greater than with free CHL. These organic-based enzyme-powered NMs represent a significant advancement in drug delivery, offering a promising approach to combat AMR while addressing the challenges of crossing complex BBs.

JTD Keywords: Bacterial infections, Biologicalbarriers, Design, Drug deliver, Enzyme, Mucu, Nanogels, Nanomotors, Nanoparticles

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

© 2020 Elsevier B.V. Semi-interpenetrated nanogels (NGs) able to release and sense diclofenac (DIC) have been designed to act as photothermal agents with the possibility to ablate cancer cells using mild-temperatures (<45 °C). Combining mild heat treatments with simultaneous chemotherapy appears as a very promising therapeutic strategy to avoid heat resistance or damaging the surrounding tissues. Particularly, NGs consisted on a poly(N-isopropylacrylamide) (PNIPAM) and dendritic polyglycerol (dPG) mesh containing a semi-interpenetrating network (SIPN) of poly(hydroxymethyl 3,4-ethylenedioxythiophene) (PHMeEDOT). The PHMeEDOT acted as photothermal and conducting agent, while PNIPAM-dPG NG provided thermoresponsivity and acted as stabilizer. We studied how semi-interpenetration modified the physicochemical characteristics of the thermoresponsive SIPN NGs and selected the best condition to generate a multifunctional photothermal agent. The thermoswitchable conductiveness of the multifunctional NGs and the redox activity of DIC could be utilized for its electrochemical detection. Besides, as proof of the therapeutic concept, we investigated the combinatorial effect of photothermal therapy (PTT) and DIC treatment using the HeLa cancer cell line in vitro. Within 15 min NIR irradiation without surpassing 45 °C we were able to kill 95% of the cells, demonstrating the potential of SIPN NGs as drug carriers, sensors and agents for mild PTT.

JTD Keywords: cells, cellulose, conducting polymers, controlled delivery, diclofenac, efficiency, electrochemical oxidation, electrochemical sensors, nanogels, nanoparticles, photothermal therapy, pnipam, poly(3,4-ethylenedioxythiophene), Conducting polymers, Electrochemical sensors, Nanogels, Photothermal therapy