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Macromolecular permeability across the blood-nerve and blood-brain barriers.

The permeability of insulin (Ins), nerve growth factor (NGF), albumin (Alb), transferrin (Trf), and IgG across the blood-nerve barrier (BNB) … to 66-fold higher than for Alb, whether this reflects receptor-mediated uptake, adsorptive-mediated transcytosis, or some other mechanism is unclear. That the PS values for NGF and Trf differ from Alb and IgG clearly suggests, however, a different uptake mechanism. Finally, the remarkably high PS values for Ins across the BBB and BNB identify this protein and …

Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo.

Dendrimers are highly branched macromolecules of low polydispersity that provide many exciting opportunities for design of novel drug-carriers, gene delivery systems and imaging agents. They hold promise in tissue targeting applications, controlled drug release and moreover, their interesting nanoscopic architecture might allow easier passage across biological barriers by transcytosis. However, from the vast array of structures currently emerging from synthetic chemistry it is essential to design molecules that have real potential for in vivo biological use. Here, polyamidoamine (PAMAM, Starbu…

DT(270-326) , a Truncated Diphtheria Toxin, Increases Blood-Tumor Barrier Permeability by Upregulating the Expression of Caveolin-1.

AIM: The nontoxic mutant of diphtheria toxin (DT) has been demonstrated to act as a receptor-specific carrier protein to delivery drug into brain. Recent research showed that the truncated "receptorless" DT was still capable of being internalized into cells. This study investigated the effects and potential mechanisms of DT(270-326) , a truncated "receptorless" DT, on the permeability of the blood-tumor barrier (BTB). METHODS: BTB and GECs were subjected to DT(270-326) treatment. HRP flux assays, immunofluorescent, co-immunoprecipitation, Western blot, CCK-8, and Flow cytometry analysis were

Intranasal Introduction of Fc-Fused Interleukin-7 Provides Long-Lasting Prophylaxis against Lethal Influenza Virus Infection.

UNLABELLED: Influenza A virus (IAV) infection frequently causes hospitalization and mortality due to severe immunopathology. Annual vaccination and antiviral drugs are the current countermeasures against IAV infection, but they have a limited efficacy against new IAV variants. Here, we show that intranasal pretreatment with Fc-fused interleukin-7 (IL-7-mFc) protects mice from lethal IAV infections. The protective activity of IL-7-mFc relies on transcytosis via neonatal Fc receptor (FcRn) in the lung and lasts for several weeks. Introduction of IL-7-mFc alters pulmonary immune environments, lea…

Cerebrovascular and blood-brain barrier impairments in Huntington's disease: Potential implications for its pathophysiology.

OBJECTIVE: Although the underlying cause of Huntington's disease (HD) is well established, the actual pathophysiological processes involved remain to be fully elucidated. In other proteinopathies such as Alzheimer's and Parkinson's diseases, there is evidence for impairments of the cerebral vasculature as well as the blood-brain barrier (BBB), which have been suggested to contribute to their pathophysiology. We investigated whether similar changes are also present in HD. METHODS: We used 3- and 7-Tesla magnetic resonance imaging as well as postmortem tissue analyses to assess blood vessel imp

Nanobiotechnology-based drug delivery in brain targeting.

Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disor … therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity of specific receptors expressed across the BBB. It is found that the low density lipoproteins related protein (LPR) with engineered peptide compound (EpiC) formed the platform incorporating the Angiopep peptide as a new effective therapeuti …

New concepts in extracellular signaling for insulin action: the single gateway hypothesis.

Insulin resistance is a precursor to and primary cause of Type 2 diabetes mellitus. In addition, insulin resistance is associated with other … tions-evidence supports a nonspecific mechanism of transport across endothelium (i.e., diffusion or transcytosis). Transendothelial transport alters the in vivo patterns of insulin signaling-biphasic plasma insulin after glucose injection is reflected in a simple, rapid increase in interstitial insulin to an elevated concentration. The time course of insulin's …

Доставка липосомных лекарств для лечения неврологических расстройств: достижения и проблемы.

Методы доставки липосомных наркотиков становятся все более жизнеспособными вариантами улучшения результатов лечения неврологических заболеваний. Эти системы обеспечивают гибкую основу для разработки лекарств, предназначенных для доставки в мозг, защиты лекарств от энзиматического расстройства и расширения их биодоступности. Для обеспечения максимального взаимодействия между липосом и наркотиком и повышения эффективности доставки, ориентированного на мозг, используются различные стратегии формулирования, такие, как модификация поверхности и дистанционное загрузка. Используя различные пути для п

Совпадение в аннотации оригинала
Liposomal drug delivery methods are becoming increasingly viable options for improving treatment outcomes for neurological illnesses. These … pathways to cross the blood- -brain barrier (BBB), such as passive diffusion and receptor-mediated transcytosis, liposomes facilitate the effective transport of therapeutic drugs to the brain parenchyma. Liposomal formulations show potential for targeted drug delivery, reducing off-target effects, and improving treatment efficacy in neurological conditions li …

In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells.

Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression

Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters.

OBJECTIVE: Hydroxyurea has proven laboratory and clinical therapeutic benefits for sickle cell anemia and other diseases, yet many questions remain about its in vivo pharmacokinetic and pharmacodynamic profiles. Previous reports suggest that hydroxyurea passively diffuses across cells, but its observed rapid absorption and distribution are more consistent with facilitated or active transport. We investigated the potential role of solute carrier (SLC) transporters in cellular uptake and accumulation of hydroxyurea. MATERIALS AND METHODS: Passive diffusion of hydroxyurea across cell membranes w

Characterization of a HIR-Fab-IDS, Novel Iduronate 2-Sulfatase Fusion Protein for the Treatment of Neuropathic Mucopolysaccharidosis Type II (Hunter Syndrome).

BACKGROUND: Mucopolysaccharidosis type II is a severe lysosomal storage disease caused by deficient activity of the enzyme iduronate-2-sulfa … the HIR-Fab-IDS crossing the blood-brain barrier owing to internalization of the hybrid molecule by transcytosis into endothelial cells adjacent to the nervous system by the principle of a 'molecular Trojan horse'. OBJECTIVES: In this work, the physicochemical and biological characterization of a blood-brain barrier-penetrating fusion protein, HIR-Fab-IDS, is …

In vitro interactions between aged garlic extract and drugs used for the treatment of cardiovascular and diabetic patients.

BACKGROUND: Disease preventing effects gained by garlic consumption have been recognized since early period of history, making commercially available garlic supplements attractive to the general public. Possible pharmacokinetic interactions which could occur between applied drugs and aged garlic extract (AGE) are unknown. AIM: To test in vitro impact of some garlic phytochemicals on P-glycoprotein (Pgp), the most recognized efflux transporter, and the effect of AGE on passive membrane permeability, absorptive and secretory intestinal transporters. METHODS: Rat small intestine and Caco-2 cell

New prospects for 89Zr-immuno-PET in brain applications - Alpha-synucleinopathies.

BACKGROUND: Recently, 89Zr-immuno-PET imaging of therapeutic antibodies, actively transported over the blood-brain-barrier via transferrin-mediated transcytosis, was demonstrated using the chelator DFO*. In these studies, aducanumab targeting amyloid-beta was fused with a transferrin binding unit: a single-chain Fab fragment derived from 8D3 (scFab8D3). Alpha-synuclein is a hallmark protein of several neurodegenerative diseases such as Parkinson's Disease, Lewy-Body-Dementia, and Multiple System Atrophy. 89Zr-immuno-PET imaging of alpha-synuclein can be a valuable tool for image-guided drug de…

Liposomes for the Treatment of Brain Cancer-A Review.

Due to their biocompatibility, non-toxicity, and surface-conjugation capabilities, liposomes are effective nanocarriers that can encapsulate chemotherapeutic drugs and facilitate targeted delivery across the blood-brain barrier (BBB). Additionally, strategies have been explored to synthesize liposomes that respond to internal and/or external stimuli to release their payload controllably. Although research into liposomes for brain cancer treatment is still in its infancy, these systems have great potential to fundamentally change the drug delivery landscape. This review paper attempts to consol

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… The transport modes of nanocarriers targeted at the BBB can be broadly categorized into four groups: transporter-mediated transcytosis (TMT), receptor-mediated endocytosis (RME), receptor-mediated transcytosis (RMT), and adsorptive-mediated transcytosis (AMT). … Following intravenous injection into the monkey brain, the HIRMAb facilitated the transcytosis of the liposome containing the foreign gene across the BBB and the endocytosis across the neuronal plasma membrane. …

Эгоистические нейрофармацевтики: открытие кровеносного барьера для лечения следующего поколения.

Блокирование мозга крови (ББД) представляет собой огромную проблему в нейрофармакологии, ограничивая доставку терапевтических агентов в мозг. Экзосомы, нанокарьеры природы, стали многообещающим решением из-за их биосовместимости, низкой иммуногенности и врожденной способности пересекать ББД. Тщательное изучение анатомии и физиологии ББД свидетельствует о сложности доставки неврологических наркотиков и подчеркивает ограниченность традиционных методов. В настоящем обзоре изучается потенциал нейрофармацевтики с экзосомной силой, при этом особое внимание уделяется их структурным и функциональным с

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… These vesicles are subsequently trafficked to late endosomes or lysosomes for degradation or undergo sorting for transcytosis across endothelial cells [ 68 ]. … This process is further influenced by integrin signaling, which modulates endothelial permeability and enhances transcytosis efficiency [ 75 ]. …

Repositioning of drugs for Parkinson's disease and pharmaceutical nanotechnology tools for their optimization.

Parkinson's disease (PD) significantly affects patients' quality of life and represents a high economic burden for health systems. Given the lack of safe and effective treatments for PD, drug repositioning seeks to offer new medication alternatives, reducing research time and costs compared to the traditional drug development strategy. This review aimed to collect evidence of drugs proposed as candidates to be reused in PD and identify those with the potential to be reformulated into nanocarriers to optimize future repositioning trials. We conducted a detailed search in PubMed, Web of Science,

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… Thus, the efficacy of NPs in PD can be improved by functionalizing the surface with Lf and Tf that act as ligands to promote receptor-mediated transcytosis (Fig. 4 b). Fig. 4 a Increased specificity towards BBB. … The passage through the BBB is exemplified through receptor-mediated transcytosis. …

Воздействие метаболического синдрома на нейроинфламму и мозговой барьер.

Метаболический синдром, который включает диабет и ожирение. one из самых распространенных медицинских заболеваний. Она вызывает системное воспаление, приводящее к далеко идущим последствиям для тела, которое все еще обнаруживается. Neuropathology, вызванная метаболическим синдромом, часто является результатом повышения проницаемости кровеносного мозга (ББД). ББД, система, предназначенная для ограничения проникновения токсинов, иммунных клеток и патогенов в мозг, имеет жизненно важное значение для надлежащей нейронной функции. Местное и системное воспаление, вызванное ожирением или типом 2 Мели

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… Due to a lack of plasmalemma vesicles, brain ECs have very low rates of transcytosis ( Ben-Zvi et al., 2014 ; Andreone et al., 2017 ; Chow and Gu, 2017 ). They display low expression of leukocyte adhesion molecules (LAMs) and of ligand-specific transporters. … Transcytosis is also altered, together with downregulation of P -glycoprotein, leptin, and amino acid transporters ( Ransohoff et al., 2015 ), but upregulation of influx transporters for TNF-α, lysosomal enzymes, Aβ, and monoamines ( Varatharaj and Galea, 2017 ). …

Эффективность Куркумина в нейродегенеративных болезнях: от фармакокинетических барьеров до передовых систем доставки.

Предыстория и цели: Основные нейродегенеративные заболевания (НД) - болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS) и амиотропический боковой склероз (ALS) - создают растущее бремя для здоровья людей во всем мире при отсутствии доступных методов лечения, позволяющих вести борьбу с заболеваниями. Куркумин, полифенол из Curcuma longa, является многообещающим кандидатом из-за его плейотропного антиоксиданта, антивоспалительного и нейрозащитного профиля, наблюдаемого главным образом в доклинических моделях, но плохой оральной биодоступности ().<1%) и незначительное пр

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… To provide a comprehensive overview of the strategies currently available for curcumin delivery across the blood–brain barrier (BBB), Figure 4 summarizes the six main transport routes: passive diffusion, carrier-mediated transport (CMT), receptor-mediated transcytosis (RMT), adsorptive-mediated transcytosis … ; MSC, mesenchymal stem cell; NPs, nanoparticles; PD, Parkinson’s disease; PLGA, poly(lactic-co-glycolic acid); RMT, receptor-mediated transcytosis; scFv, single-chain variable fragment; SLN, solid lipid nanoparticles; TfR, transferrin receptor; TJs, tight junctions. 4.7. …

Delivery of Drugs into Cancer Cells Using Antibody-Drug Conjugates Based on Receptor-Mediated Endocytosis and the Enhanced Permeability and Retention Effect.

Innumerable people worldwide die of cancer every year, although pharmaceutical therapy has actualized many benefits in human health. For background, anti-cancer drug development is difficult due to the multifactorial pathogenesis and complicated pathology of cancers. Cancer cells excrete hydrophobic low-molecular anti-cancer drugs by overexpressed efflux transporters such as multiple drug resistance 1 (MDR1) at the apical membrane. Mutation-driven drug resistance is also developed in cancer. Moreover, the poor distribution of drug to cancer cells is a serious problem, because patients suffer f

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… Smart Strategies for Therapeutic Agent Delivery into Brain across the Blood-Brain Barrier Using Receptor-Mediated Transcytosis. Chem. Pharm. Bull. 2020;68:316–325. doi: 10.1248/cpb.c19-00854. 7. Tashima T. … Delivery of Intravenously Administered Antibodies Targeting Alzheimer’s Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis. Pharmaceutics. 2022;14:411. doi: 10.3390/pharmaceutics14020411. 10. Tashima T. …

Advancing Medulloblastoma Treatment: Molecular Mechanisms, Drug Repurposing, and Precision Therapies.

Medulloblastomas are the most common malignant pediatric brain tumors, representing approximately 20% of the central nervous system cancers in children. These tumors are highly heterogeneous and classified into four molecular subgroups-WNT, SHH, Group 3, and Group 4-each with distinct genetic and epigenetic profiles that influence tumor behavior, therapeutic response, and patient outcomes. Advances in molecular diagnostics have improved the subclassification of medulloblastomas, yet treatment outcomes for high-risk subtypes, particularly Group 3, remain poor, with current modalities often asso

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… Receptor-mediated transcytosis strategies, such as paclitaxel conjugated with Angiopep-2 targeting LRP1 , have been explored in phase II trials, although some candidates such as GRN1005 were discontinued because of limited efficacy [ 44 ]. … Crossing the blood–brain barrier: innovations in receptor- and transporter-mediated transcytosis strategies. Pharmaceutics. 2025;17(6):706. 40574019 10.3390/pharmaceutics17060706 PMC12196388 45. …