Nasal administration of drugs as a new non-invasive strategy for efficient treatment of multiple sclerosis

There are several approaches to treat ocular diseases, which can be invasive or non-invasive. Within the non-invasive, new pharmaceutical strategies based on nanotechnology and mucoadhesive polymers are emerging methodologies, which aim to reach an efficient treatment of eye diseases. The aim of this work was the development of novel chitosan/hyaluronic acid nanoparticle systems with mucoadhesive properties, intended to encapsulate antioxidant molecules (e.g., crocin) aiming to reduce eye oxidative stress and, consequently, ocular disease. An ultraviolet (UV) absorber molecule, actinoquinol, was also added to the nanoparticles, to further decrease oxidative stress. The developed nanoparticles were characterized and the results showed a mean particle size lower than 400 nm, polydispersity index of 0.220 ± 0.034, positive zeta potential, and high yield. The nanoparticles were also characterized in terms of pH, osmolality, and viscosity. Mucoadhesion studies involving the determination of zeta potential, viscosity, and tackiness, showed a strong interaction between the nanoparticles and mucin. In vitro release studies using synthetic membranes in Franz diffusion cells were conducted to unravel the drug release kinetic profile. Ex vitro studies using pig eye scleras in Franz diffusion cells were performed to evaluate the permeation of the nanoparticles. Furthermore, in vitro assays using the ARPE-19 (adult retinal pigment epithelium) cell line showed that the nanoparticles can efficiently decrease oxidative stress and showed low cytotoxicity. Thus, the developed chitosan/hyaluronic acid nanoparticles are a promising system for the delivery of antioxidants to the eye, by increasing their residence time and controlling their delivery.

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Liposome Photosensitizer Formulations for Effective Cancer Photodynamic Therapy

Pharmaceutics ◽

10.3390/pharmaceutics13091345 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1345

Author(s):

Sherif Ashraf Fahmy ◽

Hassan Mohamed El-Said Azzazy ◽

Jens Schaefer

Keyword(s):

Reactive Oxygen Species ◽

Photodynamic Therapy ◽

Adverse Effects ◽

Cellular Uptake ◽

Treatment Effectiveness ◽

State Of The Art ◽

Oxygen Species ◽

Chemotherapeutic Drugs ◽

Invasive Strategy ◽

Non Invasive

Photodynamic therapy (PDT) is a promising non-invasive strategy in the fight against that which circumvents the systemic toxic effects of chemotherapeutics. It relies on photosensitizers (PSs), which are photoactivated by light irradiation and interaction with molecular oxygen. This generates highly reactive oxygen species (such as 1O2, H2O2, O2, ·OH), which kill cancer cells by necrosis or apoptosis. Despite the promising effects of PDT in cancer treatment, it still suffers from several shortcomings, such as poor biodistribution of hydrophobic PSs, low cellular uptake, and low efficacy in treating bulky or deep tumors. Hence, various nanoplatforms have been developed to increase PDT treatment effectiveness and minimize off-target adverse effects. Liposomes showed great potential in accommodating different PSs, chemotherapeutic drugs, and other therapeutically active molecules. Here, we review the state-of-the-art in encapsulating PSs alone or combined with other chemotherapeutic drugs into liposomes for effective tumor PDT.

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Eye movement evaluation in Multiple Sclerosis and Parkinson’s Disease using a Standardized Oculomotor and Neuro-ophthalmic Disorder Assessment (SONDA)

10.1101/2020.04.20.20072603 ◽

2020 ◽

Author(s):

Alessandro Grillini ◽

Remco J. Renken ◽

Anne C. L. Vrijling ◽

Joost Heutink ◽

Frans W. Cornelissen

Keyword(s):

Multiple Sclerosis ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Standardized Tests ◽

Eye Movement ◽

Oculomotor System ◽

Oculomotor Behavior ◽

Non Invasive ◽

Spatio Temporal ◽

Pursuit Gain

AbstractEvaluating the state of the oculomotor system of a patient is one of the fundamental tests done in neuro-ophthalmology. However, up to date, very few quantitative standardized tests of eye movements quality exist, limiting this assessment to confrontational tests reliant on subjective interpretation. Furthermore, quantitative tests relying on eye movement properties such as pursuit gain and saccade dynamics are often insufficient to capture the complexity of the underlying disorders and are often (too) long and tiring. In this study, we present SONDA (Standardised Oculomotor and Neurological Disorder Assessment): this test is based on analyzing eye tracking recorded during a short and intuitive continuous tracking task. We tested patients affected by Multiple Sclerosis (MS) and Parkinson’s Disease (PD) and find that: (1) the saccadic dynamics of the main sequence alone are not sufficient to separate patients from healthy controls; (2) the combination of spatio-temporal and statistical properties of saccades and saccadic dynamics enables an identification of oculomotor abnormalities in both MS and PD patients. We conclude that SONDA constitutes a powerful screening tool that allows an in-depth evaluation of (deviant) oculomotor behavior in a few minutes of non-invasive testing.

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Objective duplex ultrasound evaluation of the extracranial circulation in multiple sclerosis patients undergoing venoplasty of internal jugular vein stenoses: A pilot study

Phlebology The Journal of Venous Disease ◽

10.1177/0268355513515473 ◽

2013 ◽

Vol 30 (2) ◽

pp. 98-104 ◽

Cited By ~ 12

Author(s):

P Thibault ◽

W Lewis ◽

S Niblett

Keyword(s):

Multiple Sclerosis ◽

Blood Flow ◽

Cerebral Perfusion ◽

Objective Assessment ◽

Duplex Ultrasound ◽

Additional Parameter ◽

Non Invasive ◽

Venous Circulation ◽

Ultrasound Evaluation ◽

Multiple Sclerosis Patients

Objective Chronic cerebrospinal venous insufficiency (CCSVI) is a condition associated with multiple sclerosis (MS) and manifested by stenoses in the extracranial venous circulation. There is a need for an objective non-invasive assessment of CCSVI that is able to accurately identify the location of stenoses and quantify physiological changes in blood flows following treatment. Method A duplex ultrasound method, extracranial duplex ultrasound (ECDU), is described where the internal jugular veins (IJVs) and vertebral veins (VVs) were examined in the supine and sitting position before and after venoplasty in eight patients with clinically diagnosed MS. High-resolution B-mode imaging was used to detect obvious stenoses, intra-luminal membranes, valve abnormalities and vein wall thickening. ECDU was then used to assess blood flow including reflux. To assess obstruction, venous blood volume flows (BVFs) were taken bilaterally from the proximal (J1), mid (J2) and distal (J3) segments of the IJVs and the mid cervical VVs. To assess cerebral perfusion, bilateral BVF measurements were taken, in the supine position only, from the proximal internal carotid arteries (ICA) and mid cervical vertebral arteries (VA). The global arterial cerebral blood flow (GACBF) was then calculated as the sum of the ICA and VA measurements. Results Pre-venography ECDU detected IJV stenoses or obstruction in all patients. Venography findings were consistent with those of the pre-treatment ECDU with the exception of the detection of bilateral IJV stenoses in two patients diagnosed with unilateral IJV stenosis by ECDU. A significant improvement in GACBF was evident following venoplasty ( p < 0.05). A trend to improvement in the post-treatment BVFs of both the IJVs and the mid cervical VVs was also observed. This improvement was most marked in the left VVs ( p = 0.052) and the J2 segment of right IJVs ( p < 0.05). Conclusion The ECDU examination described provides a reliable objective assessment of IJV and VV stenoses and, with the use of BVFs, can quantify the degree of obstruction. These results support the use of ECDU as a non-invasive post-operative assessment of the success of venoplasty. The ability of ECDU to measure GACBF provides an additional parameter to monitor vascular pathophysiology in MS patients. The current findings support the view that the early symptomatic benefits observed after venoplasty for stenoses in the extracranial venous circulation may be the result of increased cerebral perfusion.

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