Enhanced Doxorubicin Delivery to the Brain Administered Through Glutathione PEGylated Liposomal Doxorubicin (2B3-101) as Compared with Generic Caelyx,®/Doxil®—A Cerebral Open Flow Microperfusion Pilot Study

Birngruber, Thomas; Raml, Reingard; Gladdines, Werner; Gatschelhofer, Christina; Gander, Edgar; Ghosh, Arijit; Kroath, Thomas; Gaillard, Pieter J.; Pieber, Thomas R.; Sinner, Frank

doi:10.1002/jps.23994

Cited by 93 publications

(61 citation statements)

References 20 publications

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“…A beneficial influence from the GSH-PEG liposomes was also indicated when a different approach with cerebral open-flow microperfusion (cOFM) was used to study doxorubicin (16). Reasons for the different results between studies may be caused by differences with regard to the (drug) molecules and the liposomal composition.…”

Section: Discussionmentioning

confidence: 97%

“…Encapsulation of methylprednisolone in the GSHcoated PEG liposomes improved its therapeutic efficacy in acute experimental autoimmune encephalomyelitis (EAE) in mice compared to that of the drug in non-coated PEG liposomes (14). GSH-PEG liposomes containing doxorubicin also appear to be effective according to preclinical and Phase I clinical cancer trials, and are currently under investigation in a Phase II study (clinicaltrials.gov NCT01386580, NCT01818713) (15,16). Similarly structured PEGylated liposomes have been shown to be a safe, effective drug delivery system in cancer treatment and have been on the market for many years, e.g., containing doxorubicin as the active compound (Doxil®/Caelyx®) (17,18).…”

Section: Introductionmentioning

confidence: 97%

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In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes

Lindqvist

Rip²,

Kregten³

et al. 2015

Pharm Res

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes

Lindqvist

Rip²,

Kregten³

et al. 2015

Pharm Res

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“…GSH-PEGylated liposomes have been effectively applied as a brain drug delivery platform for the improvement of numerous treatments. One of the most developed GSH-liposomes is 2B3-101, which is PEGylated liposomal doxorubicin modified with GSH for the treatment of multiple brain cancer indications [15]. We have prepared liposomes with surface coating by GSH in this study.…”

Section: Discussionmentioning

confidence: 99%

“…It has antioxidant-like characteristics and is readily transported across the BBB [13]. Recent reports have demonstrated that GSH can be used as a targeting ligand linked to PEGylated nanoparticles to improve delivery of therapeutics to CNS [14,15]. Among different approaches, the most advanced is 2B3-101, which is a liposomal doxorubicin formulation coated with GSH and PEG.…”

Section: Introductionmentioning

confidence: 99%

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Enhancing Anticancer Effect of Gefitinib across the Blood–Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80

Lin¹,

Hong²,

Wang³

et al. 2016

IJMS

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood–brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd.3 cells. Gefitinib was encapsulated in small unilamellar liposomes modified with glutathione (GSH) and Tween 80 (SUV-G+T; one ligand plus one surfactant) or RF (SUV-RF; one α-helical cell-penetrating peptide). GSH, Tween 80, and RF were tested by the sulforhodamine B (SRB) assay to find their non-cytotoxic concentrations on bEnd.3 cells. The enhancement on gefitinib across the BBB was evaluated by cytotoxicity assay on human lung adenocarcinoma PC9 cells under the bEnd.3 cells grown on the transwell inserts. Our findings showed that gefitinib incorporated in SUV-G+T or SUV-RF across the bEnd.3 cells significantly reduced the viability of PC9 cells more than that of free gefitinib. Furthermore, SUV-RF showed no cytotoxicity on bEnd.3 cells and did not affect the transendothelial electrical resistance (TEER) and transendothelial permeability of sodium fluorescein across the BBB model. Moreover, flow cytometry and confocal laser scanning microscopy were employed to evaluate the endocytosis pathways of SUV-RF. The results indicated that the uptake into bEnd.3 cells was mainly through adsorptive-mediated mechanism via electrostatic interaction and partially through clathrin-mediated endocytosis. In conclusion, cell penetrating peptide-conjugated SUV-RF shed light on improving drug transport across the BBB via modulating the transcytosis pathway(s).

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Nanomaterials‐Mediated Structural and Physiological Modulation of Blood Brain Barrier for Therapeutic Purposes

Ghouri

Saleem

Ren

et al. 2021

Adv Materials Inter

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Blood brain barrier (BBB) protects homeostasis and sensitive environment of brain from several toxic substances coming from the systemic circulation. This barrier along with those substances also prevents therapeutic chemicals to reach brain tissues for several brain diseases. BBB consists of a number of cell types and junctions that help maintain its intricate structure and physiology. To open BBB for therapeutic purposes, researchers are keen to explore the use of nanomaterials as therapeutic agents. Nanomaterials have unique physio‐chemical properties such as, increased surface area to mass ratio, superior adsorption capacity, and a wide variety of functionalization possibilities in contrast to bulk materials, making them sought‐after for research pertaining to brain delivery of therapeutic substances. Both organic and inorganic nanomaterials have been researched in this regard with numerous interesting functionalizations, and their toxicity and distribution profiles have been well assessed. Different pathways taken up by nanomaterials to cross BBB like adsorptive‐mediated transcytosis, inhibition of active efflux pumps, receptor‐mediated transport, and cell‐mediated endocytosis have also been investigated. This review summarizes the structural and physiological properties and the modulation techniques of BBB for delivery of adsorbed/functionalized nano delivery platforms and imaging nanomaterials across.

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Enhanced Doxorubicin Delivery to the Brain Administered Through Glutathione PEGylated Liposomal Doxorubicin (2B3-101) as Compared with Generic Caelyx,®/Doxil®—A Cerebral Open Flow Microperfusion Pilot Study

Cited by 93 publications

References 20 publications

In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes

In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes

Enhancing Anticancer Effect of Gefitinib across the Blood–Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80

Nanomaterials‐Mediated Structural and Physiological Modulation of Blood Brain Barrier for Therapeutic Purposes

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