Magnetic hydrogels for levodopa release and cell stimulation triggered by external magnetic field.

Magnetic responsive hydrogels composed of alginate (Alg) and xanthan gum (XG), crosslinked with Ca2+ ions, were modified by in situ magnetic nanoparticles (MNP) formation. In comparison to magnetic Alg hydrogels, magnetic Alg-XG hydrogels presented superior mechanical and swelling properties, due to the high charge density and molecular weight of XG. The loading efficiency of levodopa (LD), an important antiparkinson drug, in the Alg-XG/MNP hydrogels was the highest (64%), followed by Alg/MNP (56%), Alg-XG (53%) and Alg (28%). A static external magnetic field (EMF) of 0.4 T stimulated the release of LD from Alg-XG/MNP hydrogels achieving 64 ±â€¯6% of the initial loading after 30 h. The viability, proliferation and expression of dopaminergic markers of human neuroblastoma SH-SY5Y cell on the LD loaded magnetic hydrogels were successful, particularly under EMF, which stimulated the release of LD. Overall, the results of this study provided the rational design of magnetic hydrogels for the delivery of drugs, which combined with external magnetic stimulus, might improve cell proliferation and specific differentiation.

Alginate/magnetite hybrid beads for magnetically stimulated release of dopamine.

Hybrid beads composed of magnetite nanoparticles (MNP) and alginate (Alg) were synthesized and coded as Alg-MNP. They were incubated in dopamine (DOPA) solution (5 g/L), at pH 7.4 and 8 °C, during 12 h, promoting the DOPA loaded magnetic beads, coded as Alg-MNP/DOPA. The release of DOPA was further evaluated in the absence and the presence of external magnetic field (EMF) of 0.4 T. The products Alg-MNP and Alg-MNP/DOPA were characterized by scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS), Fourier transform infrared vibrational spectroscopy (FTIR), UV spectrophotometry, thermogravimetric analyses (TGA), inductively coupled plasma atomic emission spectroscopy (ICP-AES) analyses and superconducting quantum interference device (SQUID) magnetometer. The magnetic and chemical properties of Alg-MNP beads were not affected by DOPA loading. The incorporation of DOPA into the beads depended on the pH and on the negative charge density. At pH 7.4 38% of DOPA were loaded into Alg-MNP beads, whereas at pH 2 or using neat Alg beads (lower charge density than Alg-MNP) the loading efficiency decreased to one third or less. In the absence of EMF, 24% of the loaded DOPA was released from Alg-MNP at pH 7.4 over a period of 26 h. The released amount increased to 33% under the stimulus of EMF. A model was proposed to explain the loading efficiency of charged drugs, as DOPA, into hybrid beads and the role played by EMF on delivery systems, where drug and matrix are oppositely charged. The results suggest that the alginate combined with magnetite nanoparticles is a promising system for release of DOPA in the presence of EMF.

[Levodopa for Parkinson's disease: What have we learned?]. / Levodopa en la enfermedad de Parkinson: Qué hemos aprendido?

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Dopamine deficit is the cornerstone of its clinical manifestations. Levodopa, the main treatment for this condition, was first used for PD more than 40 years ago and today it still is the most powerful treatment for this disease. In recent years many advances have been made for understanding of the neurochemical mechanisms of this drug. Furthermore, new insights about the genesis of motor complications secondary to its use are known, specially related with the mode of its administration. This article updates the pharmacology of levodopa and its implications for the pathophysiology and treatment of PD. The new available presentations of levodopa are also reviewed. The implications of these advances for the treatment of this disease are commented.

Levodopa en la enfermedad de Parkinson: ¿Qué hemos aprendido? / Levodopa for Parkinson's disease: What have we learned?

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Dopamine deficit is the cornerstone of its clinical manifestations. Levodopa, the main treatment for this condition, was first used for PD more than 40 years ago and today it still is the most powerful treatment for this disease. In recent years many advances have been made for understanding of the neurochemical mechanisms of this drug. Furthermore, new insights about the genesis of motor complications secondary to its use are known, specially related with the mode of its administration. This article updates the pharmacology of levodopa and its implications for the pathophysiology and treatment of PD. The new available presentations of levodopa are also reviewed. The implications of these advances for the treatment of this disease are commented.

Study of the biodistribution of the amantadine labelled with technetium-99m in Wistar female rats.

Amantadine (AMA) has been described as dopamine stimulant and norepineprhine release, capable to block the N-methyl-D aspartate (NMDA) glutamatergic and nicotinic receptors, enhancing the sexual behavior of the male rats and inducing hypersexuality in humans. The use of technetium-99m (99mTc) can be justified for its physical and chemical properties. The aim of this study was to label and evaluate the bioavailability of the AMA labelled with 99mTc (99mTc-AMA) in Wistar female rats. The solution of 99mTc-AMA was administered by intraperitoneal way and the animals were sacrificed in CO2 chamber 10 min after the administration of the radiotracer. Various organs were removed, weighted, their radioactivity was determined using an auto-gamma counter and the results were expressed as the percentage of the injected activity per gram of tissue (%ATI/g). In the control group only Na99mTcO4 was administered. The analysis of results shows that the highest uptakes 99mTc-AMA treated group were: ovary (7.11 +/- 1.43), spleen (3.54 +/- 1.05), thyroid (2.67 +/- 0.15), stomach (1.56 +/- 1.10), duodenum (0.87 +/- 0.52), muscular tissue (0.57 +/- 0.06), liver (0.52 +/- 0.25), and at control group: thyroid (16.45 +/- 2.57), ovary (1.28 +/- 0.12), liver (1.10 +/- 0.04), spleen (0.57 +/- 0.07) and muscular tissue (0.26 +/- 0.03). The results obtained suggest that 99mTc-AMA may be used to study the bioavailability of amantadine and evaluate its effect in sexual behavior in female rats.

Efectos de la clozapina sobre diferentes receptores / Clozapine effects on different receptors

Los experimentos se realizaron, con el propósito de valorar el efecto de la clozapina sobre los receptores a dopamina, norepinefrina, glutámico, GABA y acetilcolina. Se encontró, que los desplasamientos fueron principalmente y en orden de importancia, en los receptores M1/M2 de acetilcolina, y en los receptores a dopamina; los efectos encontrados en glutámico y GABA fueron principalmente en la corteza frontal y no se observo inhibición en la unión de norepinefrina por clozapina en ninguna área estudiada. Esto sugiere una participación importante de la corteza frontal, así como la presencia de estos receptores analizados, los cuales presentan una gran homología molecular, lo que habrá que estudiar desde diferentes puntos de vista