The use of magnetic nanoparticles in hyperthermia, that is, heating induced by alternating magnetic fields, is gaining interest as a non-invasive, free of side effects technique that can be ...considered as a co-adjuvant of other cancer treatments. Having sufficient control on the field characteristics, within admissible limits, the focus is presently on the magnetic material. In the present contribution, no attempt has been made of using other composition than superparamagnetic iron oxide nanoparticles (SPION), or of applying surface functionalization, which opens a wider range of choices. We have used a hydrothermal synthesis route that allows preparing SPION nanoparticles in the 40 nm size range, with spherical, cuboidal or rod-like shapes, by minor changes in the synthesis steps. The three kinds of particles (an attempt to produce star-shaped colloids yielded hematite) were demonstrated to have the magnetite (or maghemite) crystallinity. Magnetization cycles showed virtually no hysteresis and demonstrated the superparamagnetic nature of the particles, cuboidal ones displaying saturation magnetization comparable to bulk magnetite, followed by rods and spheres. The three types were used as hyperthermia agents using magnetic fields of 20 kA/m amplitude and frequency in the range 136-205 kHz. All samples demonstrated to be able to raise the solution temperature from room values to 45 °C in a mere 60 s. Not all of them performed the same way, though. Cuboidal magnetic nanoparticles (MNPs) displayed the maximum heating power (SAR or specific absorption rate), ranging in fact among the highest reported with these geometries and raw magnetite composition.
Nanomaterials provide enormous opportunities to overcome the limitations of conventional ocular delivery systems, such as low therapeutic efficacy, side effects due to the systemic exposure, or ...invasive surgery. Apart from the more common ocular disorders, there are some genetic diseases, such as cystic fibrosis, that develop ocular disorders as secondary effects as long as the disease progresses. These patients are more difficult to be pharmacologically treated using conventional drug routes (topically, systemic), since specific pharmacological formulations can be incompatible, display increased toxicity, or their therapeutic efficacy decreases with the administration of different kind of chemical molecules. Magnetic nanoparticles can be used as potent drug carriers and magnetic hyperthermia agents due to their response to an external magnetic field. Drugs can be concentrated in the target point, limiting the damage to other tissues. The other advantage of these magnetic nanoparticles is that they can act as magnetic resonance imaging agents, allowing the detection of the exact location of the disease. However, there are some drawbacks related to their use in drug delivery, such as the limitation to maintain efficacy in the target organ once the magnetic field is removed from outside. Another disadvantage is the difficulty in maintaining the therapeutic action in three dimensions inside the human body. This review summarizes all the application possibilities related to magnetic nanoparticles in ocular diseases.
Gelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility, easy processability, transparency, non-toxicity, and reasonable ...mechanical properties to mimic the extracellular matrix (ECM). Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application. We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor, utilizing epoxide ring-opening reactions and visible light-crosslinking. This chemical modification allows the obtaining of an elastic protein-based hydrogel (GELGYM) with excellent biomimetic properties, approaching those of the native tissue. GELGYM can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95 MPa with compressive strains as high as 80% compared to Gelatin-methacryloyl (GeIMA), the most studied derivative of gelatin used as a bioadhesive. GELGYM is also highly biocompatible and supports cellular adhesion, proliferation, and migration in both 2 and 3-dimensional cell-cultures. These characteristics along with its super adhesion to biological tissues such as cornea, aorta, heart, muscle, kidney, liver, and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation, tissue adhesive, wound dressing, bioprinting, and drug and cell delivery.
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•Gelatin based adhesives have been used in the last decades in different biomedical applications.•Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application.•We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor.•Epoxide ring-opening reactions and visible light-crosslinking allows the obtaining of an elastic gelatin-based hydrogel (GELGYM).•GELGYM shows excellent biomimetic properties, approaching those of the native tissue.
Corneal mechanical changes are believed to occur before any visible structural alterations observed during routine clinical evaluation. This study proposed developing an elastography technique based ...on torsional waves (TWE) adapted to the specificities of the cornea. By measuring the displacements in the propagation plane perpendicular to the axis of the emitter, the effect of guided waves in plate-like media was proven negligible. Ex vivo experiments were carried out on porcine corneal samples considering a group of control and one group of alkali burn treatment (Formula: see textOH) that modified the mechanical properties. Phase speed was recovered as a function of intraocular pressure (IOP), and a Kelvin-Voigt rheological model was fitted to the dispersion curves to estimate viscoelastic parameters. A comparison with uniaxial tensile testing with thin-walled assumptions was also performed. Both shear elasticity and viscosity correlated positively with IOP, being the elasticity lower and the viscosity higher for the treated group. The viscoelastic parameters ranged from 21.33 to 63.17 kPa, and from 2.82 to 5.30 Pa s, for shear elasticity and viscosity, respectively. As far as the authors know, no other investigations have studied this mechanical plane under low strain ratios, typical of dynamic elastography in corneal tissue. TWE reflected mechanical properties changes after treatment, showing a high potential for clinical diagnosis due to its rapid performance time and paving the way for future in vivo studies.
Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies (HEMT), including elexacaftor-tezacaftor-ivacaftor, correct the underlying molecular defect ...causing CF. HEMT decreases general symptom burden by improving clinical metrics and quality of life for most people with CF (PwCF) with eligible CFTR variants. This has resulted in more pregnancies in women living with CF. All HEMT are known to be able pass through the placenta and into breast milk in mothers who continue on this therapy while pregnant and breast feeding. Toxicity studies of HEMT in young rats demonstrated infant cataracts, and case reports have reported the presence of congenital cataracts in early life exposure to HEMT. This article reviews the evidence for how HEMT influences the dynamic and interdependent processes of healthy and abnormal lens development in the context of HEMT exposure during pregnancy and breastfeeding, and raises questions that remain unanswered.
Pulmonary drug delivery has long been used for local and systemic administration of different medications used in acute and chronic respiratory diseases. Certain lung diseases, such as cystic ...fibrosis, rely heavily on chronic treatments, including targeted lung delivery. Pulmonary drug delivery possesses various physiological advantages compared to other delivery methods and is also convenient for the patient to use. However, the formulation of dry powder for pulmonary delivery proves challenging due to aerodynamic restrictions and the lower tolerance of the lung. The aim of this review is to provide an overview of the respiratory tract structure in patients with cystic fibrosis, including during acute and chronic lung infections and exacerbations. Furthermore, this review discusses the advantages of targeted lung delivery, including the physicochemical properties of dry powder and factors affecting clinical efficacy. Current inhalable drug treatments and drugs currently under development will also be discussed.
Ivacaftor-lumacaftor and ivacaftor are two new breakthrough cystic fibrosis transmembrane conductance modulators. The interactions of ivacaftor and its two metabolites hydroxymethylivacaftor (iva-M1) ...and ivacaftorcarboxylate (iva-M6) with neurotransmitter receptors were investigated in radioligand binding assays. Ivacaftor displayed significant affinity to the 5-hydroxytryptamine (5-HT; serotonin) 5-HT
receptor (p
=6.06±0.03), β
-adrenergic receptor (p
=5.71±0.07), δ-opioid receptor (p
=5.59±0.06) and the dopamine transporter (p
=5.50±0.20); iva-M1 displayed significant affinity to the 5-HT
receptor (p
=5.81±0.04) and the muscarinic M3 receptor (p
=5.70±0.10); iva-M6 displayed significant affinity to the 5-HT
receptor (p
=7.33±0.05). The
central nervous system activity of ivacaftor (40 mg·kg
intraperitoneally for 21 days) was assessed in a chronic mouse model of depression. In the forced swim test, the ivacaftor-treated group displayed decreased immobility (52.8±7.6 s), similarly to fluoxetine (33.8±11.0 s), and increased climbing/swimming activity (181.5±9.2 s). In the open field test, ivacaftor produced higher locomotor activity than the fluoxetine group, measured both as mean number of paw touches (ivacaftor 81.1±9.6
fluoxetine 57.9±9.5) and total distance travelled (ivacaftor 120.6±16.8 cm
fluoxetine 84.5±16.0 cm) in 600 s. Treatment of 23 cystic fibrosis patients with ivacaftor-lumacaftor resulted in significant improvements in quality of life (including anxiety) in all five domains of the AweScoreCF questionnaire (p=0.092-0.096). Our findings suggest ivacaftor displays potential clinical anxiolytic and stimulating properties, and may have beneficial effects on mood.
Magnetic nanoparticles (MNPs) have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by the enhanced permeability and retention effect. ...Their incorporation into biopolymer coatings enables the preparation of magnetic field-responsive, biocompatible nanoparticles that are well dispersed in aqueous media. Here we describe a synthetic route to prepare functionalized, stable magnetite nanoparticles (MNPs) coated with a temperature-responsive polymer, by means of the hydrothermal method combined with an oil/water (o/w) emulsion process. The effects of both pH and temperature on the electrophoretic mobility and surface charge of these MNPs are investigated. The magnetite/polymer composition of these systems is detected by Fourier Transform Infrared Spectroscopy (FTIR) and quantified by thermogravimetric analysis. The therapeutic possibilities of the designed nanostructures as effective heating agents for magnetic hyperthermia are demonstrated, and specific absorption rates as high as 150 W/g, with 20 mT magnetic field and 205 kHz frequency, are obtained. This magnetic heating response could provide a promising nanoparticle system for combined diagnostics and cancer therapy.
In this paper, it is proposed that polymer-coated magnetic nanorods (MNRs) can be used with the advantage of a double objective: first, to serve as magnetic hyperthermia agents, and second, to be ...used as magnetic vehicles for the antitumor drug doxorubicin (DOX). Two different synthetic methodologies (hydrothermal and co-precipitation) were used to obtain MNRs of maghemite and magnetite. They were coated with poly(ethyleneimine) and poly(sodium 4-styrenesulfonate), and loaded with DOX, using the Layer-by-Layer technique. Evidence of the polymer coating and the drug loading was justified by ATR-FTIR and electrophoretic mobility measurements, and the composition of the coated nanorods was obtained by a thermogravimetric analysis. The nanorods were tested as magnetic hyperthermia agents, and it was found that they provided sufficiently large heating rates to be used as adjuvant therapy against solid tumors. DOX loading and release were determined by UV-visible spectroscopy, and it was found that up to 50% of the loaded drug was released in about 5 h, although the rate of release could be regulated by simultaneous application of hyperthermia, which acts as a sort of external release-trigger. Shape control offers another physical property of the particles as candidates to interact with tumor cells, and particles that are not too elongated can easily find their way through the cell membrane.
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