Improving the transport of chemotherapeutic drugs across the blood–brain barrier

Orthmann, Andrea; Fichtner, Iduna; Zeisig, Reiner

doi:10.1586/ecp.11.26

Cited by 24 publications

(19 citation statements)

References 150 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A subtle and dynamic equilibrium between both forces determines one of the main blood-brain exchange processes. Nevertheless, the paracellular diffusion only plays a minor role in the brain-targeted drugs (Orthmann et al, 2011).…”

Section: The Paracellular Pathwaymentioning

confidence: 99%

“…The transcellular pathway, which can be energy or non-energy dependent, includes transcellular diffusion across both the luminal and the abluminal membrane of the capillary endothelium (Engelhardt and Sorokin, 2009), receptor-mediated transcytosis, efflux transport system, endocytosis of positively charged molecules and carrier-mediated transport (Orthmann et al, 2011).…”

Section: The Transcellular Pathwaymentioning

confidence: 99%

“…Nanoparticles (NPs) delivery system is solid colloidal particles with dimensions within the nanometric scale (Olivier, 2005;Orthmann et al, 2011). Similar to polymeric nanocarriers it is a macromolecule build up by repetitions of simple structural units consisting of biocompatible and GRAS ingredients.…”

Section: Nanopolimers and Nanoparticlesmentioning

confidence: 99%

See 2 more Smart Citations

The blood-brain barrier: Structure, function and therapeutic approaches to cross it

Tajes

Ramos-Fernández

Weng-Jiang

et al. 2014

Molecular Membrane Biology

328

149

View full text Add to dashboard Cite

The blood-brain barrier (BBB) is constituted by a specialized vascular endothelium that interacts directly with astrocytes, neurons and pericytes. It protects the brain from the molecules of the systemic circulation but it has to be overcome for the proper treatment of brain cancer, psychiatric disorders or neurodegenerative diseases, which are dramatically increasing as the population ages. In the present work we have revised the current knowledge on the cellular structure of the BBB and the different procedures utilized currently and those proposed to cross it. Chemical modifications of the drugs, such as increasing their lipophilicity, turn them more prone to be internalized in the brain. Other mechanisms are the use of molecular tools to bind the drugs such as small immunoglobulins, liposomes or nanoparticles that will act as Trojan Horses favoring the drug delivery in brain. This fusion of the classical pharmacology with nanotechnology has opened a wide field to many different approaches with promising results to hypothesize that BBB will not be a major problem for the new generation of neuroactive drugs. The present review provides an overview of all state-of-the-art of the BBB structure and function, as well as of the classic strategies and these appeared in recent years to deliver drugs into the brain for the treatment of Central Nervous System (CNS) diseases.

show abstract

Section: The Paracellular Pathwaymentioning

confidence: 99%

Section: The Transcellular Pathwaymentioning

confidence: 99%

See 1 more Smart Citation

The blood-brain barrier: Structure, function and therapeutic approaches to cross it

Tajes

Ramos-Fernández

Weng-Jiang

et al. 2014

Molecular Membrane Biology

328

149

View full text Add to dashboard Cite

show abstract

“…The permeability of the paracellular pathway is functionally regulated (i) by the abundance of such barrier‐forming TJ proteins and (ii) by the cohesion forces exerted by AJ proteins along with underlying scaffold and cytoskeletal proteins (Zahraoui et al., ). Provided that the barrier function of this pathway is not altered, paracellular diffusion plays only a minor role in the transport of brain‐targetted drugs (Miller, ; Orthmann et al., ).…”

Section: The Bbbmentioning

confidence: 99%

Control of the blood–brain barrier function in cancer cell metastasis

Blecharz

Colla

Rohde

et al. 2015

Biology of the Cell

View full text Add to dashboard Cite

Cerebral metastases are the most common brain neoplasms seen clinically in the adults and comprise more than half of all brain tumours. Actual treatment options for brain metastases that include surgical resection, radiotherapy and chemotherapy are rarely curative, although palliative treatment improves survival and life quality of patients carrying brain-metastatic tumours. Chemotherapy in particular has also shown limited or no activity in brain metastasis of most tumour types. Many chemotherapeutic agents used systemically do not cross the blood-brain barrier (BBB), whereas others may transiently weaken the BBB and allow extravasation of tumour cells from the circulation into the brain parenchyma. Increasing evidence points out that the interaction between the BBB and tumour cells plays a key role for implantation and growth of brain metastases in the central nervous system. The BBB, as the tightest endothelial barrier, prevents both early detection and treatment by creating a privileged microenvironment. Therefore, as observed in several in vivo studies, precise targetting the BBB by a specific transient opening of the structure making it permeable for therapeutic compounds, might potentially help to overcome this difficult clinical problem. Moreover, a better understanding of the molecular features of the BBB, its interrelation with metastatic tumour cells and the elucidation of cellular mechanisms responsible for establishing cerebral metastasis must be clearly outlined in order to promote treatment modalities that particularly involve chemotherapy. This in turn would substantially expand the survival and quality of life of patients with brain metastasis, and potentially increase the remission rate. Therefore, the focus of this review is to summarise the current knowledge on the role and function of the BBB in cancer metastasis.

show abstract

“…In addition, TAT-modified micelles have been used to improve the delivery of small molecule drugs, like ciprofloxacin, across the BBB to the brain [105, 106]. SynB peptides and Angiopeps are the most extensively studied vehicles for the delivery of such drugs to the brain [107]. …”

Section: Delivery Of Therapeutic Molecules Across the Bbb Mediated Bymentioning

confidence: 99%

Cell-Penetrating Peptide-Mediated Therapeutic Molecule Delivery into the Central Nervous System

Zou

Wang³

et al. 2013

143

View full text Add to dashboard Cite

The blood-brain barrier (BBB), a dynamic and complex barrier formed by endothelial cells, can impede the entry of unwanted substances – pathogens and therapeutic molecules alike – into the central nervous system (CNS) from the blood circulation. Taking into account the fact that CNS-related diseases are the largest and fastest growing unmet medical concern, many potential protein- and nucleic acid-based medicines have been developed for therapeutic purposes. However, due to their poor ability to cross the BBB and the plasma membrane, the above-mentioned bio-macromolecules have limited use in treating neurological diseases. Finding effective, safe, and convenient ways to deliver therapeutic molecules into the CNS is thus urgently required. In recent decades, much effort has been expended in the development of drug delivery technologies, of which cell-penetrating peptides (CPPs) have the most promising potential. The present review covers the latest advances in CPP delivery technology, and provides an update on their use in CNS-targeted drug delivery.

show abstract

Improving the transport of chemotherapeutic drugs across the blood–brain barrier

Cited by 24 publications

References 150 publications

The blood-brain barrier: Structure, function and therapeutic approaches to cross it

The blood-brain barrier: Structure, function and therapeutic approaches to cross it

Control of the blood–brain barrier function in cancer cell metastasis

Cell-Penetrating Peptide-Mediated Therapeutic Molecule Delivery into the Central Nervous System

Contact Info

Product

Resources

About