The Bioavailability of Drugs—The Current State of Knowledge

Molecules, Journal Year: 2023, Volume and Issue: 28(24), P. 8038 - 8038

Published: Dec. 11, 2023

Drug bioavailability is a crucial aspect of pharmacology, affecting the effectiveness drug therapy. Understanding how drugs are absorbed, distributed, metabolized, and eliminated in patients' bodies essential to ensure proper safe treatment. This publication aims highlight relevance research its importance In addition biochemical activity, also plays critical role achieving desired therapeutic effects. may seem obvious, but it worth noting that can only produce expected effect if level concentration be achieved at point patient's body. Given differences between patients, dosages, administration forms, understanding controlling has become priority pharmacology. discusses basic concepts factors it. We looked various methods assessing bioavailability, both laboratory clinic. Notably, introduction new technologies tools this field vital achieve advances research. cases with poorly described providing deeper complex challenges they pose medical researchers practitioners. Simultaneously, article focuses on perspectives trends shape future regarding which development modern pharmacology context, offers an essential, meaningful contribution toward highlighting bioavailability's reliable patient The text identifies areas require further exploration.

Language: Английский

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Association between vascular endothelial growth factor-mediated blood–brain barrier dysfunction and stress-induced depression

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(9), P. 3822 - 3832

Published: May 26, 2022

Language: Английский

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Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

ACS Nano, Journal Year: 2024, Volume and Issue: 18(3), P. 1820 - 1845

Published: Jan. 9, 2024

The blood–brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, BBB also prevents passage of various forms therapeutic agents, nanocarriers, their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe effective vehicles in neurotheranostics. In this Review, first we introduce anatomical physiological functions BBB. Second, present endogenous exogenous transport mechanisms by NPs cross We report nanomaterials, carriers, cargos, with detailed uptake permeability characteristics. Third, describe effect regulating size, shape, charge, surface ligands affect permeability, can be exploited enhance promote classify typical functionalized nanomaterials developed for crossing. Fourth, provide comprehensive review recent progress functional polymeric applications multimodal bioimaging, therapeutics, drug delivery. Finally, conclude discussing existing directions, future perspectives employing

Language: Английский

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Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): A current overview of active targeting in brain diseases

Colloids and Surfaces B Biointerfaces, Journal Year: 2022, Volume and Issue: 221, P. 112999 - 112999

Published: Nov. 2, 2022

The blood-brain barrier (BBB) restricts the access of therapeutic agents to brain, complicating treatment neurological diseases, such as Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery central nervous system (CNS), potential nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, surface nanocarriers can be modified with ligands that interact BBB, enhancing their uptake penetration across brain endothelium by different physiological mechanisms, receptor- or transporter-mediated transcytosis. This review seeks provide an overview targeting in delivery, while highlighting functionalized lipid treat diseases. Therefore, first sections, we discuss importance CNS present commonly used for functionalization, well summarize state art most recent relevant studies surface-modified nanosystems developed disorders. Lastly, challenges hindering clinical translation are discussed, critical insights future perspectives outlined. Although some limitations have identified, it is expected upcoming years these will established approach.

Language: Английский

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Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway

International Journal of Oral Science, Journal Year: 2023, Volume and Issue: 15(1)

Published: Jan. 12, 2023

Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) essential keeping toxic substances entering tissues. However, effect of bacteremia on BBB permeability and its underlying mechanism remains unclear. In present study, rats were injected tail vein three times a week eight weeks induce bacteremia. An vitro model infected was also established. We that infiltration Evans blue dye Albumin protein deposition rat increased could pass through model. Caveolae detected after BMECs both vivo vitro. Caveolin-1 (Cav-1) expression enhanced infection. Downregulation Cav-1 rescued gingivalis-enhanced permeability. further gingivalis-gingipain be colocalized strong hydrogen bonding between arg-specific-gingipain (RgpA) detected. Moreover, significantly inhibited major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed gingivalis-increased These results revealed Mfsd2a/Cav-1 mediated transcytosis key pathway governing gingivalis, which may contribute gingivalis/virulence entrance subsequent neurological impairments.

Language: Английский

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Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(760)

Published: Aug. 14, 2024

Antisense oligonucleotides (ASOs) are promising therapeutics for treating various neurological disorders. However, ASOs unable to readily cross the mammalian blood-brain barrier (BBB) and therefore need be delivered intrathecally central nervous system (CNS). Here, we engineered a human transferrin receptor 1 (TfR1) binding molecule, oligonucleotide transport vehicle (OTV), tool ASO across BBB in TfR knockin (TfR mu/hu KI) mice nonhuman primates. Intravenous injection systemic delivery of OTV KI resulted sustained knockdown target RNA, Malat1 , multiple mouse CNS regions cell types, including endothelial cells, neurons, astrocytes, microglia, oligodendrocytes. In addition, enabled RNA quadriceps cardiac muscles, which difficult with alone. Systemically more uniform biodistribution profile greater compared bivalent, high-affinity antibody. cynomolgus macaques, an directed against MALAT1 displayed robust primate intrathecal dosing same unconjugated ASO. Our data support systemically as potential platform delivering therapeutic BBB.

Language: Английский

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Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis

Chemical Science, Journal Year: 2024, Volume and Issue: 15(6), P. 1966 - 2006

Published: Jan. 1, 2024

Neoplasias pose a significant threat to aging society, underscoring the urgent need overcome limitations of traditional chemotherapy through pioneering strategies. Targeted drug delivery is an evolving frontier in cancer therapy, aiming enhance treatment efficacy while mitigating undesirable side effects. One promising avenue utilizes cell membrane receptors like folate receptor guide transporters precisely malignant cells. Based on cellular as hallmark, targeted nanocarriers and small molecule-drug conjugates have been developed that comprise different (bio) chemistries and/or mechanical properties with individual advantages challenges. Such modern folic acid-conjugated stimuli-responsive provide systemic controlled release, enabling reduced dosages, circumvention resistance, diminished adverse Since transporters' structure-based

Language: Английский

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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

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Effect of Nanoparticle Composition, Size, Shape, and Stiffness on Penetration Across the Blood–Brain Barrier

ACS Biomaterials Science & Engineering, Journal Year: 2020, Volume and Issue: 6(9), P. 4916 - 4928

Published: Aug. 17, 2020

The delivery of therapeutics to the brain in an efficient, noninvasive manner continues be a major unmet need field drug delivery. One significant impediment results from existence physical yet dynamic blood–brain barrier (BBB). Despite many, often complex strategies that currently exist breach BBB, adequate effective bloodstream remain quite low. Nanotechnology has emerged as promising tool for delivery, but little is known about important particle parameters influence Here, we synthesized and characterized library nanoparticles with distinct properties ranging size, shape, stiffness, composition investigate identify key attributes influencing uptake transport To accomplish this task, vitro human BBB model was developed validated using cerebral microvascular endothelial cells (hCMEC/D3). Particle apparent permeability coefficients (Papp) were then determined each group. elucidate roles different on across predominant mechanisms endocytosis also investigated. Our show yielded greatest impact penetration model. This work lays foundation provides new insights into role BBB.

Language: Английский

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Drug Delivery Across The Blood–Brain Barrier: Recent Advances in The Use of Nanocarriers

Nanomedicine, Journal Year: 2020, Volume and Issue: 15(2), P. 205 - 214

Published: Jan. 1, 2020

The blood–brain barrier (BBB) has a significant contribution to homeostasis and protection of the CNS. However, it also limits crossing therapeutics thereby complicates treatment CNS disorders. To overcome this limitation, use nanocarriers for drug delivery across BBB recently been exploited. Nanocarriers can utilize different physiological mechanisms be modified achieve desired kinetics efficacy. Consequentially, several have reported act as functional nanomedicines in preclinical studies using animal models human diseases. Given rapid development novel nanocarriers, review provides comprehensive insight into most recent advancements made nanocarrier-based CNS, such multifunctional theranostics.

Language: Английский

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