Assessment of Different Niosome Formulations for Optogenetic Applications: Morphological and Electrophysiological Effects.

Gene therapy and optogenetics are becoming promising tools for treating several nervous system pathologies. Currently, most of these approaches use viral vectors to transport the genetic material inside the cells, but viruses present some potential risks, such as marked immunogenicity, insertional mutagenesis, and limited insert gene size. In this framework, non-viral nanoparticles, such as niosomes, are emerging as possible alternative tools to deliver genetic material, avoiding the aforementioned problems.

Long-term biophysical stability of nanodiamonds combined with lipid nanocarriers for non-viral gene delivery to the retina.

Nanodiamonds were combined with niosome, and resulting formulations were named as nanodiasomes, which were evaluated in terms of physicochemical features, cellular internalization, cell viability and transfection efficiency both in in vitro and in in vivo conditions. Such parameters were analyzed at 4 and 25 C, and at 15 and 30 days after their elaboration. Nanodiasomes showed a particle size of 128 nm that was maintained over time inside the ± 10% of deviation, unless after 30 days of storage at 25 °C.

Toward a personalized closed-loop stimulation of the visual cortex: Advances and challenges.

Current cortical visual prosthesis approaches are primarily unidirectional and do not consider the feed-back circuits that exist in just about every part of the nervous system. Herein, we provide a brief overview of some recent developments for better controlling brain stimulation and present preliminary human data indicating that closed-loop strategies could considerably enhance the effectiveness, safety, and long-term stability of visual cortex stimulation. We propose that the development of improved closed-loop strategies may help to enhance our capacity to communicate with the brain.

Impaired macroglial development and axonal conductivity contributes to the neuropathology of DYRK1A-related intellectual disability syndrome.

The correct development and activity of neurons and glial cells is necessary to establish proper brain connectivity. DYRK1A encodes a protein kinase involved in the neuropathology associated with Down syndrome that influences neurogenesis and the morphological differentiation of neurons. DYRK1A loss-of-function mutations in heterozygosity cause a well-recognizable syndrome of intellectual disability and autism spectrum disorder.

Time stability and connectivity analysis with an intracortical 96-channel microelectrode array inserted in human visual cortex.

Microstimulation via electrodes that penetrate the visual cortex creates visual perceptions called phosphenes. Besides providing electrical stimulation to induce perceptions, each electrode can be used to record the brain signals from the cortex region under the electrode which contains brain state information. Since the future visual prosthesis interfaces will be implanted chronically in the visual cortex of blind people, it is important to study the long-term stability of the signals acquired from the electrodes.

Nanodiamond Integration into Niosomes as an Emerging and Efficient Gene Therapy Nanoplatform for Central Nervous System Diseases.

Nanodiamonds (NDs) are promising materials for gene delivery because of their unique physicochemical and biological features, along with their possibility of combination with other nonviral systems. Our aim was to evaluate the biophysical performance of NDs as helper components of niosomes, named nanodiasomes, to address a potential nonviral gene delivery nanoplatform for therapeutic applications in central nervous system (CNS) diseases. Nanodiasomes, niosomes, and their corresponding complexes, obtained after genetic material addition at different ratios (w/w), were evaluated in terms of physicochemical properties, cellular uptake, intracellular disposition, biocompatibility, and transfection efficiency in HEK-293 cells.

Machine Learning Method for Functional Assessment of Retinal Models.

Challenges in the field of retinal prostheses motivate the development of retinal models to accurately simulate Retinal Ganglion Cells (RGCs) responses. The goal of retinal prostheses is to enable blind individuals to solve complex, reallife visual tasks. In this paper, we introduce the functional assessment (FA) of retinal models, which describes the concept of evaluating the performance of retinal models on visual understanding tasks.

Using Biologically-inspired Image Features to Model Retinal Response: Evidence from Biological Datasets.

Retinal models are needed to simulate the translation of visual percepts to Retinal Ganglion Cells (RGCs) neural spike trains, through which visual information is transmitted to the brain. Restoring vision through neural prostheses motivates the development of accurate retinal models. We integrate biologically-inspired image features to RGC models.

Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex.

BACKGROUNDA long-held goal of vision therapy is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists.METHODSWe implanted an intracortical microelectrode array consisting of 96 electrodes in the visual cortex of a 57-year-old person with complete blindness for a 6-month period.

Sphingolipid extracts enhance gene delivery of cationic lipid vesicles into retina and brain.

The aim was to evaluate relevant biophysic processes related to the physicochemical features and gene transfection mechanism when sphingolipids are incorporated into a cationic niosome formulation for non-viral gene delivery to central nervous system. For that, two formulations named niosphingosomes and niosomes devoid of sphingolipid extracts, as control, were developed by the oil-in water emulsion technique. Both formulations and the corresponding complexes, obtained upon the addition of the reporter EGFP plasmid, were physicochemically and biologically characterized and evaluated.

Development of a Prodrug of Camptothecin for Enhanced Treatment of Glioblastoma Multiforme.

A novel therapeutic approach for glioblastoma multiforme (GBM) therapy has been carried out through and testing by using the prodrug camptothecin-20--(5-aminolevulinate) (CPT-ALA). The incorporation of ALA to CPT may promote uptake of the cytotoxic molecule by glioblastoma cells where the heme synthesis pathway is active, improving the therapeutic action and reducing the side effects over healthy tissue. The antitumor properties of CPT-ALA have been tested on different GBM cell lines (U87, U251, and C6) as well as in an orthotopic GBM model in rat, where potential toxicity in central nervous system cells was analyzed.

Neurolight: A Deep Learning Neural Interface for Cortical Visual Prostheses.

Visual neuroprosthesis, that provide electrical stimulation along several sites of the human visual system, constitute a potential tool for vision restoration for the blind. Scientific and technological progress in the fields of neural engineering and artificial vision comes with new theories and tools that, along with the dawn of modern artificial intelligence, constitute a promising framework for the further development of neurotechnology. In the framework of the development of a Cortical Visual Neuroprosthesis for the blind (CORTIVIS), we are now facing the challenge of developing not only computationally powerful tools and flexible approaches that will allow us to provide some degree of functional vision to individuals who are profoundly blind.

Brain Angiogenesis Induced by Nonviral Gene Therapy with Potential Therapeutic Benefits for Central Nervous System Diseases.

Gene therapy employing nanocarriers represents a promising strategy to treat central nervous system (CNS) diseases, where brain microvasculature is frequently compromised. Vascular endothelial growth factor (VEGF) is a key angiogenic molecule; however, its administration to the CNS by nonviral gene therapy has not been conducted. Hence, we prepared and physicochemically characterized four cationic niosome formulations (-), which were combined with pVEGF-GFP to explore their capacity to transfer the VEGF gene to CNS cells and achieve angiogenesis in the brain.

The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson's Disease.

MicroRNAs (miRNAs) are small double-stranded RNAs that exert a fine-tuning sequence-specific regulation of cell transcriptome. While one unique miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by various miRNAs that bind to complementary sequences at 3'-untranslated regions for triggering the mechanism of RNA interference. Unfortunately, dysregulated miRNAs play critical roles in many disorders, including Parkinson's disease (PD), the second most prevalent neurodegenerative disease in the world.

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues.

Non-viral vectors have emerged as a promising alternative to viral gene delivery systems due to their safer profile. Among non-viral vectors, recently, niosomes have shown favorable properties for gene delivery, including low toxicity, high stability, and easy production. The three main components of niosome formulations include a cationic lipid that is responsible for the electrostatic interactions with the negatively charged genetic material, a non-ionic surfactant that enhances the long-term stability of the niosome, and a helper component that can be added to improve its physicochemical properties and biological performance.

Gene delivery to the rat retina by non-viral vectors based on chloroquine-containing cationic niosomes.

The incorporation of chloroquine within nano formulations, rather than as a co-treatment of the cells, could open a new avenue for in vivo retinal gene delivery. In this manuscript, we evaluated the incorporation of chloroquine diphosphate into the cationic niosome formulation composed of poloxamer 188, polysorbate 80 non-ionic surfactants, and 2,3-di (tetradecyloxy) propan-1-amine (hydrochloride salt) cationic lipid, to transfect rat retina. Niosome formulations without and with chloroquine diphosphate (DPP80, and DPP80-CQ, respectively) were prepared by the reverse phase evaporation technique and characterized in terms of size, PDI, zeta potential, and morphology.

Non-viral vectors based on cationic niosomes and minicircle DNA technology enhance gene delivery efficiency for biomedical applications in retinal disorders.

Low transfection efficiency is a major challenge to overcome in non-viral approaches to reach clinical practice. Our aim was to explore new strategies to achieve more efficient non-viral gene therapies for clinical applications and in particular, for retinal diseases. Cationic niosomes and three GFP-encoding genetic materials consisting on minicircle (2.

A 3D Convolutional Neural Network to Model Retinal Ganglion Cell's Responses to Light Patterns in Mice.

Deep Learning offers flexible powerful tools that have advanced our understanding of the neural coding of neurosensory systems. In this work, a 3D Convolutional Neural Network (3D CNN) is used to mimic the behavior of a population of mice retinal ganglion cells in response to different light patterns. For this purpose, we projected homogeneous RGB flashes and checkerboards stimuli with variable luminances and wavelength spectrum to mimic a more naturalistic stimuli environment onto the mouse retina.

Gene transfer to rat cerebral cortex mediated by polysorbate 80 and poloxamer 188 nonionic surfactant vesicles.

Background: Gene therapy can be an intriguing therapeutic option in wide-ranging neurological disorders. Though nonviral gene carriers represent a safer delivery system to their viral counterparts, a thorough design of such vehicles is crucial to enhance their transfection properties.

Purpose: This study evaluated the effects of combined use of two nonionic surfactants, poloxamer 188 (P) and polysorbate 80 (P80) into nanovesicles - based on 2,3-di(tetradecyloxy)propan-1-amine cationic lipid (D) - destined for gene delivery to central nervous system cells.

Non-viral vectors based on cationic niosomes as efficient gene delivery vehicles to central nervous system cells into the brain.

Development of safe and efficient non-viral vectors to deliver DNA into the CNS represents a huge challenge to face many neurological disorders. We elaborated niosomes based on DOTMA cationic lipid, lycopene "helper" lipid and polysorbate 60 as non-ionic surfactants for gene delivery to the CNS. Niosomes, and their corresponding nioplexes obtained after the addition of the pCMS-EGFP plasmid, were characterized in terms of size, charge, morphology and capacity to condense, release and protect DNA.

Delivery of miRNA-Targeted Oligonucleotides in the Rat Striatum by Magnetofection with Neuromag.

MicroRNAs (miRNAs) regulate gene expression at posttranscriptional level by triggering RNA interference. In such a sense, aberrant expressions of miRNAs play critical roles in the pathogenesis of many disorders, including Parkinson's disease (PD). Controlling the level of specific miRNAs in the brain is thus a promising therapeutic strategy for neuroprotection.

Polysorbate 20 non-ionic surfactant enhances retinal gene delivery efficiency of cationic niosomes after intravitreal and subretinal administration.

The success of non-viral vectors based on cationic niosomes for retinal gene delivery applications depends on the ability to achieve persistent and high levels of transgene expression, ideally from a single administration. In this work, we studied the effect of the non-ionic surfactant component of niosomes in their transfection efficiency in rat retina. For that purpose, three niosome formulations that only differed in the non-ionic tensioactives were elaborated.

WITHDRAWN: Non-viral vectors based on cationic niosomes as efficient gene delivery vehicles to central nervous system cells into the brain.

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