by Keyword: Controlled release

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Puiggalí-Jou, A., del Valle, L. J., Alemán, C., (2019). Drug delivery systems based on intrinsically conducting polymers Journal of Controlled Release 309, 244-264

This work provides an overview of the up to date research related to intrinsically conducting polymers (ICPs) and their function as novel drug delivery systems (DDSs). Drugs administrated to patients do not always reach the targeted organ, which may affect other tissues leading to undesired side-effects. To overcome these problems, DDSs are under development. Nowadays, it is possible to target the administration and, most importantly, to achieve a controlled drug dosage upon external stimuli. Particularly, the attention of this work focuses on the drug release upon electrical stimuli employing ICPs. These are well-known organic polymers with outstanding electrical properties similar to metals but also retaining some advantageous characteristics normally related to polymers, like mechanical stability and easiness of processing. Depending on the redox state, ICPs can incorporate or release anionic or cationic molecules on-demand. Besides, the releasing rate can be finely tuned by the type of electrical stimulation applied. Another interesting feature is that ICPs are capable to sense redox molecules such as dopamine, serotonin or ascorbic acid among others. Therefore, future prospects go towards the design of materials where the releasing rate could be self-adjusted in response to changes in the surrounding environment. This recompilation of ideas and projects provides a critic outline of ICPs synthesis progress related to their use as DDSs. Definitely, ICPs are a very promising branch of DDSs where the dose can be finely tuned by the exertion of an external stimulus, hence optimizing the repercussions of the drug and diminishing its side effects.

Keywords: Controlled release, DDS, Drug delivery, Electrical stimuli, ICP, Intrinsically conducting polymers

Llopis-Lorente, A., Garcií-Fernández, A., Murillo-Cremaes, N., Hortelão, A. C., Patinño, T., Villalonga, R., Sancenón, F., Martínez-Máñer, R., Sánchez, S., (2019). Enzyme-powered gated mesoporous silica nanomotors for on-command intracellular payload delivery ACS Nano 13, (10), 12171-12183

The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nanomotors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nanoparticles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy)3]Cl2 (bpy = 2,2′-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both [Ru(bpy)3]Cl2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to “sense” the environment and deliver the payload on demand in response to predefined stimuli.

Keywords: Controlled release, Drug delivery, Enzymatic catalysis, Gatekeepers, Nanocarriers, Nanomotors, Stimuli-responsive nanomaterials