Recent advances in the brain targeting of neuropharmaceuticals by chemical delivery systems

Bodor, Nicholas; Buchwald, Péter

doi:10.1016/s0169-409x(98)00090-8

Cited by 145 publications

(84 citation statements)

References 125 publications

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“…The blood-CSF barrier was considered to be similar to the blood-ELF barrier in the aspects that the capillary wall is fenestrated in both structures and epithelial cell linings of the barriers (alveolar cell lining and choroidal epithelial lining) are sealed with tight junctions (46,89). Most studies investigating drug penetration to the central nervous system have been performed with brain tissue (2,13,16,17,40,48,49,56,59,68,71,76,84,95). However, the blood-brain barrier (BBB) is different from blood-CSF and blood-ELF barriers in that the brain capillary wall is not fenestrated and endothelial cells are also sealed with tight junctions.…”

Section: Discussionmentioning

confidence: 99%

“…It is not known whether these mechanisms are present also in the ELF epithelium. Even for passive diffusion through the BBB, many other equations have been evaluated (13,17,59,68,76,95). Although the equation used in this review might not predict actual passive penetration of drugs through the alveolar epithelium exactly, it is still believed to reflect the general concept that passive diffusion through cells depends on lipophilicity and MW.…”

Section: Discussionmentioning

confidence: 99%

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Interpretation of Antibiotic Concentration Ratios Measured in Epithelial Lining Fluid

Kiem¹,

Schentag²

2008

Antimicrob Agents Chemother

234

267

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interpretation of Antibiotic Concentration Ratios Measured in Epithelial Lining Fluid

Kiem¹,

Schentag²

2008

Antimicrob Agents Chemother

234

267

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“…So the advantages of lipophilic analogs for brain delivery might be offset by the change of drug pharmacokinetic parameters. 14 …”

Section: Lipophilic Analogsmentioning

confidence: 99%

“…As shown in Figure 5, 1,4-dihydro-N-methylnicotinic acid (dihydrotrigonelline) is a commonly used lipophilic targetor moiety that can increase the brain distribution of a wide variety of drugs. [14][15][16][17][18][19] …”

mentioning

confidence: 99%

Current approaches to enhance CNS delivery of drugs across the brain barriers

Lu¹,

Zhao²,

Wong³

et al. 2014

IJN

275

168

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Although many agents have therapeutic potentials for central nervous system (CNS) diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed.

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“…5 Several drug delivery systems were developed to bypass the BBB specifically for the treatment of neurodegenerative diseases (Alzheimer's disease and Parkinson's disease) and brain cancer, but with limited success. [6][7][8] Also majority of drugs do not have the desirable physicochemical characteristics, such as high lipid solubility, low molecular size, hydrophilic compounds, and/or positive charges, which are necessary to allow passage across the BBB. 5 These obstacles have resulted in an emphasis on developing alternative delivery modalities based on local delivery of drugs directly to the brain interstitium, particularly focused on treating brain cancer (glioma) and neurodegenerative disorders.…”

Section: Introductionmentioning

confidence: 99%

Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain

Gulati

Aw²,

Lošić

2012

IJN

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Abstract:The blood-brain barrier (BBB) blocks the passage of active molecules from the blood which makes drug delivery to the brain a challenging problem. Oral drug delivery using chemically modified drugs to enhance their transport properties or remove the blocking of drug transport across the BBB is explored as a common approach to address these problems, but with limited success. Local delivery of drugs directly to the brain interstitium using implants such as polymeric wafers, gels, and catheters has been recognized as a promising alternative particularly for the treatment of brain cancer (glioma) and neurodegenerative disorders. The aim of this study was to introduce a new solution by engineering a drug-releasing implant for local drug delivery in the brain, based on titanium (Ti) wires with titania nanotube (TNT) arrays on their surfaces. Drug loading and drug release characteristics of this system were explored using two drugs commonly used in oral brain therapy: dopamine (DOPA), a neurotransmitter agent; and doxorubicin (DOXO), an anticancer drug. Results showed that TNT/Ti wires could provide a considerable amount of drugs (.170 µg to 1000 µg) with desirable release kinetics and controllable release time (1 to several weeks) and proved their feasibility for use as drug-releasing implants for local drug delivery in the brain. Purpose: In this report, a new drug-releasing platform in the form of nanoengineered Ti wires with TNT arrays is proposed as an alternative for local delivery of chemotherapeutics in the brain to bypass the BBB. To prove this concept, drug loading and release characteristics of two drugs important for brain therapy (the neurotransmitter DOPA and the anticancer drug DOXO) were explored. Methods: Titania nanotube arrays on the surface of Ti wires (TNT/Ti) were fabricated using a simple anodization process, followed by separate loading of two drugs (DOPA and DOXO) inside the nanotube structures. The loading and in vitro release characteristics of prepared TNT/ Ti implants were examined using thermogravimetric analysis (TGA) UV-Vis spectroscopy. Results: Scanning electron microscopy studies confirmed that well-ordered, vertically aligned, densely packed nanotube arrays with an average diameter of 170 nm and length 70 µm were formed on the surface of TNT/Ti wires. TGA results showed a total drug loading of 170 µg and 1200 µg inside the TNTs for DOPA and DOXO respectively. Two-phase drug release behavior was observed including a fast release (burst) for the first 6 hours and a prolonged slow release phase for 8 days, both with acceptable dosage and desirable release kinetics. The physical, structural, loading and release characteristics of prepared TNT/Ti implants showed several advantages in comparison with existing and clinically proved brain implants. Conclusion: Our results confirmed that TNT/Ti wires can be successfully employed as a suitable platform to release neurotransmitters such as DOPA and anticancer drugs such as DOXO. Hence, they are a feasible alternative as drug-releasing ...

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Recent advances in the brain targeting of neuropharmaceuticals by chemical delivery systems

Cited by 145 publications

References 125 publications

Interpretation of Antibiotic Concentration Ratios Measured in Epithelial Lining Fluid

Interpretation of Antibiotic Concentration Ratios Measured in Epithelial Lining Fluid

Current approaches to enhance CNS delivery of drugs across the brain barriers

Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain

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