scholarly journals Liposomal Formulations for Nose-to-Brain Delivery: Recent Advances and Future Perspectives

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 540 ◽  
Author(s):  
Soon-Seok Hong ◽  
Kyung Taek Oh ◽  
Han-Gon Choi ◽  
Soo-Jeong Lim
Keyword(s):  
Drug Transport ◽  
Drug Carrier ◽  
Systemic Circulation ◽  
Direct Access ◽  
Comprehensive Overview ◽  
Transport Pathways ◽  
Therapeutic Compounds ◽  
Intranasal Drug Administration ◽  
The Impact ◽  
The Brain

Restricted drug entry to the brain that is closely associated with the existence of the blood brain barrier (BBB) has limited the accessibility of most potential active therapeutic compounds to the brain from the systemic circulation. Recently, evidences for the presence of direct nose-to-brain drug transport pathways have been accumulated by several studies and an intranasal drug administration route has gained attention as a promising way for providing direct access to the brain without the needs to cross to the BBB. Studies aiming for developing nanoparticles as an intranasal drug carrier have shown considerable promise in overcoming the challenges of intranasal drug delivery route. This review gives a comprehensive overview of works having investigated liposomes as a potential vehicle to deliver drugs to the brain through nose-to-brain route while considering the excellent biocompatibility and high potential of liposomes for clinical development. Herein, studies are reviewed with special emphasis on the impact of formulation factors, such as liposome composition and surface modification of liposomes with targeting moieties, in addition to intranasal environmental factors that may affect the extent/site of absorption of intranasally administered, liposome-encapsulated drugs.

scholarly journals Efflux-Mediated Resistance to New Oxazolidinones and Pleuromutilin Derivatives inEscherichia coliwith Class Specificities in the Resistance-Nodulation-Cell Division-Type Drug Transport Pathways

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Sabine Schuster ◽  
Martina Vavra ◽  
Winfried V. Kern
Keyword(s):  
Escherichia Coli ◽  
Cell Division ◽  
Drug Transport ◽  
Binding Pocket ◽  
Entrance Channel ◽  
Transport Pathways ◽  
Double Mutation ◽  
Content Type ◽  
Rnd Transporter ◽  
The Impact

ABSTRACTA major contribution of the resistance-nodulation-cell division (RND)-transporter AcrB to resistance to oxazolidinones and pleuromutilin derivatives inEscherichia coliwas confirmed. However, we discovered significant differences in efflux inhibitor activities, specificities of the homologous pump YhiV (MdtF), and the impact of AcrB pathway mutations. Particularly, entrance channel double-mutation I38F I671T and distal binding pocket mutation F615A revealed class-specific transport routes of oxazolidinones and pleuromutilin derivatives. The findings could contribute to the understanding of the RND-type multidrug transport pathways.

scholarly journals Understanding Drug Delivery to the Brain Using Liposome-Based Strategies: Studies that Provide Mechanistic Insights Are Essential

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Firda Juhairiyah ◽  
Elizabeth C. M. de Lange
Keyword(s):  
Drug Delivery ◽  
Drug Transport ◽  
Animal Studies ◽  
Time Course ◽  
Liposomal Formulation ◽  
Liposomal Drug ◽  
Brain Drug Delivery ◽  
Liposomal Formulations ◽  
The Impact ◽  
The Brain

AbstractBrain drug delivery may be restricted by the blood-brain barrier (BBB), and enhancement by liposome-based drug delivery strategies has been investigated. As access to the human brain is limited, many studies have been performed in experimental animals. Whereas providing interesting data, such studies have room for improvement to provide mechanistic insight into the rate and extent of specifically BBB transport and intrabrain distribution processes that all together govern CNS target delivery of the free drug. This review shortly summarizes BBB transport and current liposome-based strategies to overcome BBB transport restrictions, with the emphasis on how to determine the individual mechanisms that all together determine the time course of free drug brain concentrations, following their administration as such, and in liposomes. Animal studies using microdialysis providing time course information on unbound drug in plasma and brain are highlighted, as these provide the mechanistic information needed to understand BBB drug transport of the drug, and the impact of a liposomal formulations of that drug on BBB transport. Overall, these studies show that brain distribution of a drug administered as liposomal formulation depends on both drug properties and liposomal formulation characteristics. In general, evidence suggests that active transporters at the BBB, either being influx or efflux transporters, are circumvented by liposomes. It is concluded that liposomal formulations may provide interesting changes in BBB transport. More mechanistic studies are needed to understand relevant mechanisms in liposomal drug delivery to the brain, providing an improved basis for its prediction in human using animal data.

scholarly journals Convection-Enhanced Delivery in silico study for personalized brain cancer treatment

2021 ◽  
Author(s):  
Chryso Lambride ◽  
Vasileios Vavourakis ◽  
Triantafyllos Stylianopoulos
Keyword(s):  
Brain Cancer ◽  
In Silico ◽  
Drug Transport ◽  
Drug Distribution ◽  
Local Drug Delivery ◽  
Patient Specific ◽  
Convection Enhanced Delivery ◽  
Formidable Challenge ◽  
The Impact ◽  
The Brain

Abstract Brain cancer therapy remains a formidable challenge in oncology. Convection-enhanced delivery (CED) is an innovative and promising local drug delivery method for the treatment of brain cancer, overcoming the challenges of the systemic delivery of drugs to the brain. To improve our understanding about CED efficacy and drug transport, we present an in silico methodology for brain cancer CED treatment simulation. To achieve this, a three-dimensional finite element biomechanics formulation is utilized which employs patient-specific brain model representation and is used to predict the drug deposition in CED regimes. The model encompasses nonlinear biomechanics and the transport of drugs in the brain parenchyma. Drug distribution was studied under various patho-physiological conditions of the tumor, in terms of tumor vessel wall pore size and tumor tissue hydraulic conductivity as well as for drugs of various sizes, spanning from small molecules to nanoparticles. Our contribution reports for the first time the impact of the size of the vascular wall pores and that of the therapeutic agent on drug distribution during and after CED. The in silico findings provide useful insights of the spatio-temporal distribution and average drug concentration in the tumor towards an effective treatment of brain cancer.

scholarly journals Spinal vertebrae localization and analysis on disproportionality in curvature using radiography—a comprehensive review

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
Joddat Fatima ◽  
Muhammad Usman Akram ◽  
Amina Jameel ◽  
Adeel Muzaffar Syed
Keyword(s):  
Spinal Cord ◽  
Template Matching ◽  
Human Anatomy ◽  
Comprehensive Overview ◽  
Low Contrast ◽  
Active Shape Models ◽  
Harris Corner ◽  
Illumination Changes ◽  
The Central Nervous System ◽  
The Brain

AbstractIn human anatomy, the central nervous system (CNS) acts as a significant processing hub. CNS is clinically divided into two major parts: the brain and the spinal cord. The spinal cord assists the overall communication network of the human anatomy through the brain. The mobility of body and the structure of the whole skeleton is also balanced with the help of the spinal bone, along with reflex control. According to the Global Burden of Disease 2010, worldwide, back pain issues are the leading cause of disability. The clinical specialists in the field estimate almost 80% of the population with experience of back issues. The segmentation of the vertebrae is considered a difficult procedure through imaging. The problem has been catered by different researchers using diverse hand-crafted features like Harris corner, template matching, active shape models, and Hough transform. Existing methods do not handle the illumination changes and shape-based variations. The low-contrast and unclear view of the vertebrae also makes it difficult to get good results. In recent times, convolutional nnural Network (CNN) has taken the research to the next level, producing high-accuracy results. Different architectures of CNN such as UNet, FCN, and ResNet have been used for segmentation and deformity analysis. The aim of this review article is to give a comprehensive overview of how different authors in different times have addressed these issues and proposed different mythologies for the localization and analysis of curvature deformity of the vertebrae in the spinal cord.

scholarly journals Comprehensive Overview of Sleep Disorders in Patients with Chronic Liver Disease

2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Oana-Mihaela Plotogea ◽  
Madalina Ilie ◽  
Simona Bungau ◽  
Alexandru Laurentiu Chiotoroiu ◽  
Ana Maria Alexandra Stanescu ◽  
...  
Keyword(s):  
Sleep Disorders ◽  
Daily Practice ◽  
Chronic Liver ◽  
Asian Countries ◽  
Chronic Liver Diseases ◽  
Comprehensive Overview ◽  
The Usa ◽  
The Impact ◽  
Reliable Methods

The impact of sleep disorders (SDs) on patients with chronic liver diseases (CLD) is tremendous. SDs are frequently encountered among these patients and interfere with their quality of life. This review aims to present the data available so far about the prevalence, phenotypes, and proposed pathophysiological mechanisms of SDs in CLD. Moreover, we proposed to search the literature regarding the most reliable methods to assess SDs and the possible therapeutic options in patients with CLD. The main results of this review show that when it comes to prevalence, the percentages reported vary widely between studies performed among populations from the USA or Europe and those coming from Asian countries. Furthermore, it has been proven that SDs may also be present in the absence of neurocognitive disorders attributable to hepatic encephalopathy (HE), which contradicts traditional suppositions where SDs were considered part of the clinical scenario of HE. Currently, there are no specific recommendations or protocols to assess SDs in CLD patients and data about the therapeutic management are limited. Taking into consideration their impact, a protocol for diagnosing and managing SDs should be developed and included in the daily practice of hepatologists.

scholarly journals Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Blood Brain Barrier ◽  
Early Stage ◽  
Molecular Transport ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cns Drugs ◽  
The Impact ◽  
The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

scholarly journals The Impact of Bone on the Biology of Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
Gerard Karsenty
Keyword(s):  
Muscle Function ◽  
Male Fertility ◽  
Leydig Cells ◽  
Memory Loss ◽  
Age Related ◽  
Systematic Exploration ◽  
Biology Of Aging ◽  
The Impact ◽  
The Brain ◽  
Regulate Energy Metabolism

Abstract We hypothesized that bone may secrete hormones that regulate energy metabolism and reproduction. Testing this hypothesis revealed that the osteoblast-specific secreted protein osteocalcin is a hormone regulating glucose homeostasis and male fertility by signaling through a GPCR, Gprc6a, expressed in pancreatic β bells and Leydig cells of the testes. The systematic exploration of osteocalcin biology, revealed that it regulates an unexpectedly large spectrum of physiological functions in the brain and peripheral organs and that it has most features of an antigeromic molecule. As will be presented at the meeting, this body of work suggests that harnessing osteocalcin for therapeutic purposes may be beneficial in the treatment of age-related diseases such as depression, age-related memory loss and the decline in muscle function seen in sarcopenia.

scholarly journals Crosstalk between Existential Phenomenological Psychotherapy and Neurological Sciences in Mood and Anxiety Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 340
Author(s):  
Lehel Balogh ◽  
Masaru Tanaka ◽  
Nóra Török ◽  
László Vécsei ◽  
Shigeru Taguchi
Keyword(s):  
Anxiety Disorders ◽  
Biological Treatment ◽  
Sense Of Self ◽  
Phenomenological Approach ◽  
Neurological Damage ◽  
Mood And Anxiety Disorders ◽  
New Interpretation ◽  
And Behavior ◽  
The Impact ◽  
The Brain

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological sciences study the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on these functions, and their treatment. Both psychotherapy and neurological sciences deal with the brain; nevertheless, they continue to stay polarized. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss, and Viktor Frankl, and it has been committed to accounting for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose to life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological sciences, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the EPP may potentially play a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

scholarly journals Development of a patient-reported outcome measure for neck pain in military aircrew: qualitative interviews to inform design and content

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e039488
Author(s):  
Anna Dowling ◽  
Ellen Slungaard ◽  
Nicola R Heneghan
Keyword(s):  
Neck Pain ◽  
Outcome Measure ◽  
Physical Symptoms ◽  
Patient Reported Outcome ◽  
Direct Access ◽  
Specific Patient ◽  
Concept Elicitation ◽  
Patient Reported Outcome Measure ◽  
Patient Reported ◽  
The Impact

IntroductionThe prevalence of flight-related neck pain is 70% in UK fast jet pilots; much higher than the general population. The Aircrew Conditioning Programme and direct access physiotherapy exist to minimise the impact on military capability, but a population specific patient-reported outcome measure (PROM) is required to investigate the effectiveness of these. We aimed to explore the experiences of flight-related neck pain to inform the content validity and development of a population specific PROM.MethodsQualitative semistructured interviews combining phenomenological and grounded theory methods, reported using Consolidated criteria for Reporting Qualitative research guidelines. A purposive sample of 10 fast jet pilots with neck pain was recruited. Concept elicitation interviews were audio recorded, transcribed verbatim along with field notes. Data analysis involved subject and methodological expertise used a concept elicitation approach.ResultsParticipants included 10 male fast jet pilots, age 34.7 years. Identified themes included: (1) physical symptoms associated with flying activities; (2) occupational effects revealed modifications of flying, or ‘suboptimal’ performance owing to neck pain; (3) psychological effects revealed feelings or worry and (4) social and activity effects showed impact on out of work time.ConclusionPopulation-specific occupational, psychological and social factors should be considered alongside physical symptoms when managing neck pain in military aircrew. Findings support the development of a PROM specifically designed for military aircrew with neck pain.

scholarly journals Environmental Changes and Cultural Transitions in SW Iberia during the Early-Mid Holocene

2021 ◽  
Vol 11 (8) ◽  
pp. 3580
Author(s):  
Cristina Val-Peón ◽  
Juan I. Santisteban ◽  
José A. López-Sáez ◽  
Gerd-Christian Weniger ◽  
Klaus Reicherter
Keyword(s):  
Dietary Habits ◽  
Environmental Changes ◽  
Source Area ◽  
Direct Access ◽  
Special Focus ◽  
Early Neolithic ◽  
Archaeological Data ◽  
Local Resources ◽  
Climate Events ◽  
The Impact

The SW coast of the Iberian Peninsula experiences a lack of palaeoenvironmental and archaeological data. With the aim to fill this gap, we contribute with a new palynological and geochemical dataset obtained from a sediment core drilled in the continental shelf of the Algarve coast. Archaeological data have been correlated with our multi-proxy dataset to understand how human groups adapted to environmental changes during the Early-Mid Holocene, with special focus on the Mesolithic to Neolithic transition. Vegetation trends indicate warm conditions at the onset of the Holocene followed by increased moisture and forest development ca. 10–7 ka BP, after which woodlands are progressively replaced by heaths. Peaks of aridity were identified at 8.2 and 7. 5 ka BP. Compositional, textural, redox state, and weathering of source area geochemical proxies indicates abrupt palaeoceanographic modifications and gradual terrestrial changes at 8.2 ka BP, while the 7.5 ka BP event mirrors a decrease in land moisture availability. Mesolithic sites are mainly composed of seasonal camps with direct access to the coast for the exploitation of local resources. This pattern extends into the Early Neolithic, when these sites coexist with seasonal and permanent occupations located in inland areas near rivers. Changes in settlement patterns and dietary habits may be influenced by changes in coastal environments caused by the sea-level rise and the impact of the 8.2 and 7.5 ka BP climate events.

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