Photo-responsive polymeric nanocarriers for target-specific and controlled drug delivery.

Conventional drug delivery systems often have several pharmacodynamic and pharmacokinetic limitations related to their low efficacy and bad safety. It is because these traditional systems cannot always be selectively addressed to their therapeutic target sites. Currently, target-specific and controlled drug delivery is one of the foremost challenges in the biomedical field. In this context, stimuli-responsive polymeric nanomaterials have been recognized as a topic of intense research. They have gained immense attention in therapeutics - particularly in the drug delivery area - due to the ease of tailorable behavior in response to the surroundings. Light irradiation is of particular interest among externally triggered stimuli because it may be specifically localized in a contact-free manner. Light-human body interactions may sometimes be harmful due to photothermal and photomechanical reactions that lead to cell death by photo-toxicity and/or photosensitization. However, these limitations may also be overcome by the use of photo-responsive polymeric nanostructures. This review summarizes recent developments in photo-responsive polymeric nanocarriers used in the field of drug delivery systems, including nanoparticles, nanogels, micelles, nanofibers, dendrimers, and polymersomes, as well as their classification and mechanisms of drug release.

Metal ion homeostasis with emphasis on zinc and copper: Potential crucial link to explain the non-classical antioxidative properties of vitamin D and melatonin.

Metal ion homeostasis is an essential physiological mechanism necessary for achieving an adequate balance of these ions' concentrations in the different cellular compartments. This fact is of great importance because both an excess and a deficiency of cellular metal ion levels are usually equally harmful due to the exacerbated increase in oxidative stress that may occur in both cases. Metal ion homeostasis ensures an equilibrium among multiple functions associated with the body's antioxidative defense network controlled by metallic micronutrients such as zinc and copper, some of the central regulators of redox processes. These micronutrients significantly modulate the activity of some isoforms of superoxide dismutase (SOD) and other enzymes such as metallothioneins (MTs) and ceruloplasmin (CP), which are directly or indirectly involved in the regulation of redox homeostasis. Although it is well known that both melatonin (MEL) and vitamin D have important roles as natural antioxidants, often some of these effects are related to their actions on antioxidative processes dependent on metal ions. Thus, in addition to their classical antioxidative properties usually associated with mitochondrial effects, it is known that MEL and vitamin D modulate the expression and activity of Cu/Zn-dependent SOD isoforms, MTs and CP; function as copper chelators and regulate genomic and non-genomic mechanisms related to the zinc transport. This review summarizes the main findings related to the crucial participation of zinc and copper in physiological antioxidative status and their relationship with the non-classical antioxidant effects of MEL and vitamin D, suggesting a potential synergism among these four micronutrients.

Synthesis, physicochemical characterisation and biological activity of anandamide/ɛ-polycaprolactone nanoparticles obtained by electrospraying.

Drug encapsulation in nanocarriers such as polymeric nanoparticles (Nps) may help to overcome the limitations associated with cannabinoids. In this study, the authors' work aimed to highlight the use of electrospraying techniques for the development of carrier Nps of anandamide (AEA), an endocannabinoid with attractive pharmacological effects but underestimated due to its unfavourable physicochemical and pharmacokinetic properties added to its undesirable effects at the level of the central nervous system. The authors characterised physicochemically and evaluated in vitro biological activity of anandamide/ɛ-polycaprolactone nanoparticles (Nps-AEA/PCL) obtained by electrospraying in epithelial cells of the human proximal tubule (HK2), to prove the utility of this method and to validate the biological effect of Nps-AEA/PCL. They obtained particles from 100 to 900 nm of diameter with a predominance of 200-400 nm. Their zeta potential was -20 ± 1.86 mV. They demonstrated the stable encapsulation of AEA in Nps-AEA/PCL, as well as its dose-dependent capacity to induce the expression of iNOS and NO levels and to decrease the Na+/K+ ATPase activity in HK2 cells. Obtaining Nps-AEA/PCL by electrospraying would represent a promising methodology for a novel AEA pharmaceutical formulation development with optimal physicochemical properties, physical stability and biological activity on HK2 cells.

Preparation and characterization of bosentan monohydrate/ε-polycaprolactone nanoparticles obtained by electrospraying.

The electrospraying technique provides nano and microparticles that can be used as drug delivery systems. The aims of this study were, firstly, to optimize the influent parameters of electrospraying for the manufacture of a Bosentan (BOS) nanoparticulate platform, and secondly, to evaluate its physicochemical properties and in vitro biopharmaceutical behavior. Particles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TG) and Fourier transformed Infrared spectroscopy (FTIR). Drug loading, encapsulation efficiency and kinetic dissolution were determined. Additionally, Bosentan release assays at 24 and 72 h were performed in vitro to evaluate biopharmaceutical properties of nano-scaffolds by diffusion technique through dialysis bag. The nanostructures had heterogeneous sizes predominantly smaller than 550 nm and they were semicrystalline according to PXRD, indicating a partial amorphization of BOS during the encapsulation in the polymer matrix. FT-IR and DSC showed an absence of chemical interactions between BOS and ε-Polycaprolactone (PCL), suggesting that both components behaved as a physical mixture in these particles. The drug loading was 25.98%, and the encapsulation efficiency was 58.51%. Additionally, the release assays showed an extended and controlled release of BOS, in comparison to non-encapsulated BOS. These data also showed to fit with the Cubic Root kinetic dissolution. As a conclusion, we demonstrate that the use of electrospraying for the manufacture of BOS (or similar drugs) controlled release nanoplatforms would represent an interesting contribution in the development of new therapeutic alternatives for the treatment of pathologies such as pulmonary hypertension and other related diseases. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2748, 2019.

Nanotechnological Strategies as Smart ways for Diagnosis and Treatment of the Atherosclerosis.

Atherosclerosis provokes a continuous worsening of affected vessels causing a blood flow diminution with several complications and with clinical manifestations that generally appear in advanced phases of the illness. Hence, the conventional therapies are not enough because the atherosclerotic injuries are often irrevocable. For this reason, emerges the necessity to implement smart ways of drug supply and develop new therapeutic targets that decrease the advance atherosclerotic lesion. It results due to particular interest to use new tools for prevention, diagnosis, and treatment of this cardiovascular disease, thus concentrating our attention to accomplish better management on the immune system. Finally, this mini-review highlights the most recent knowledge about nanotechnology as a robust, novel and promissory therapeutic option applied to atherosclerotic pathology, nevertheless, we also alert for possible issues associated with their use.

Nanotecnología, un nuevo paradigma en el tratamiento de la aterosclerosis / Nanotechnology, a new paradigm in atherosclerosis treatment

La aterosclerosis, una conocida enfermedad arterial prevalente, ocasiona el deterioro progresivo de los vasos afectados provocando reducción del flujo sanguíneo con diversas complicaciones, y los síntomas suelen manifestarse en estadios avanzados de la enfermedad. En este sentido, las clásicas alternativas terapéuticas resultan insuficientes debido al carácter muchas veces irreversible del daño provocado. Por lo tanto, emerge la necesidad de implementar novedosas formas más eficaces para administrar fármacos y también el desarrollo de nuevas dianas terapéuticas que reduzcan la progresión de la lesión aterosclerótica. Además, resulta de especial interés la implementación de nuevas herramientas para la prevención, diagnóstico y tratamiento de esta patología cardiovascular, focalizando la atención en lograr un mejor control sobre el sistema inmunológico. En esta revisión se pone en relieve el conocimiento actual sobre la nanotecnología como una alternativa terapéutica potencial, moderna y prometedora, aplicada a la patología aterosclerótica, pero se advierte también sobre posibles complicaciones de su uso (AU)

Atherosclerosis, a known and prevalent disease, causes progressive deterioration of affected vessels, inducing a blood flow reduction with different complications, and its symptoms usually manifest in advanced stages of the disease. Therefore, the classic therapeutic alternatives are insufficient because the damages are many times irreversible. For this reason, there is a need to implement intelligent forms of drug administration and develop new therapeutic targets that reduce the progression of atherosclerotic lesion. The implementation of new tools for prevention, diagnosis and treatment of this cardiovascular disease is of special interest, focusing our attention on achieving a more effective control of the immune system. Finally, this review highlights the latest knowledge about nanotechnology as a powerful, modern, and promising therapeutic alternative applied to atherosclerotic disease, as well as warning of the potential complications with their use (AU)

Nanotechnology, a new paradigm in atherosclerosis treatment. / Nanotecnología, un nuevo paradigma en el tratamiento de la aterosclerosis.

Atherosclerosis, a known and prevalent disease, causes progressive deterioration of affected vessels, inducing a blood flow reduction with different complications, and its symptoms usually manifest in advanced stages of the disease. Therefore, the classic therapeutic alternatives are insufficient because the damages are many times irreversible. For this reason, there is a need to implement intelligent forms of drug administration and develop new therapeutic targets that reduce the progression of atherosclerotic lesion. The implementation of new tools for prevention, diagnosis and treatment of this cardiovascular disease is of special interest, focusing our attention on achieving a more effective control of the immune system. Finally, this review highlights the latest knowledge about nanotechnology as a powerful, modern, and promising therapeutic alternative applied to atherosclerotic disease, as well as warning of the potential complications with their use.