Pharmacokinetics, Brain Delivery, and Efficacy in Brain Tumor-Bearing Mice of Glutathione Pegylated Liposomal Doxorubicin (2B3-101)

Gaillard, Pieter J.; Appeldoorn, Chantal C.M.; Dorland, Rick; Kregten, Joan van; Manca, Francesca; Vugts, Daniëlle J.; Windhorst, Albert D.; Dongen, Guus A.M.S. van; Vries, Helga E. de; Maussang, David; Tellingen, Olaf van

doi:10.1371/journal.pone.0082331

Cited by 230 publications

(138 citation statements)

References 46 publications

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“…Evidence of increased brain uptake of other drugs using GSH-PEG liposomal preparations has recently been published. The use of the GSH-PEG liposomal system safely increased the brain delivery of doxorubicin in mice, resulting in inhibition of brain tumor growth and improved survival (15). Also, the efficacy of GSH-PEGylated liposomal methylprednisolone was enhanced compared to the use of non-targeted liposomes in a mice EAE model of neuroinflammation (14).…”

Section: Discussionmentioning

confidence: 99%

“…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: 99%

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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: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Additional active targeting using moieties that preferentially bind to receptors on the cerebral endothelial cells or overexpressed on brain tumor cells did indeed improve the therapeutic potential of nanomedicines due to preferential distribution to and within the brain tumor area: in all the studies with intravenously administered actively targeted nanomedicines, the median survival times were longer than their actively untargeted counterparts and noticeably longer than the untreated controls [75,[86][87][88].…”

Section: Systemic Delivery Of Nanomedicinesmentioning

confidence: 97%

Managing CNS Tumors: The Nanomedicine Approach

Aparicio-Blanco¹,

Torres-Suárez²

2017

New Approaches to the Management of Primary and Secondary CNS Tumors

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Albeit the rapidly evolving knowledge about tumor biochemistry enables various new drug molecules to be designed as treatments, malignant central nervous system (CNS) tumors remain untreatable due to the failure to expose the entire tumor to such therapeutics at pharmacologically meaningful quantities. Therefore, drug delivery in CNS tumors must be properly addressed, as otherwise, novel therapies will continue to fail. In this regard, nanomedicine poses an appealing platform for efficient drug delivery to the CNS, since it may be targeted to improve the drug availability in the site of action, which would be translated into lower drug doses and fewer side effects. Hence, the accumulation of data about the CNS physiology and their relevant receptors, the widening therapeutic armamentarium of drugs potentially useful in CNS chemotherapy and the alternative routes for administration may envisage nanomedicines as a forthcoming routine approach. Indeed, on the basis of the promising results gathered from preclinical studies of nanomedicine-based therapy both systemically and locally administered, some nanomedicines have already been approved for clinical trials in a variety of CNS tumor conditions to serve as the first steps in the translation of nanotherapy to clinic. Their outcome will steer research directions for further improvements.

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“…[50] According to the preclinical studies, 2B3-101 showed a 5-fold enhanced doxorubicin brain delivery versus PLD (Doxil ® ). [99] The company held a phase I/IIa clinical study in patients with solid tumors and brain metastases or recurrent malignant glioma. [100] Nektar develops new drug candidates by utilizing its proprietary 3D 4-armed branched PEGylation and advanced polymer conjugate technologies to modify the chemical structure of various active pharmaceutical ingredients.…”

Section: Solid Lipid Nanoparticlesmentioning

confidence: 99%

Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

ElAmrawy¹,

Othman²,

Adkins³

et al. 2016

JCMT

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Worldwide, the incidence of primary brain tumors is on the rise. Unfortunately, noninvasive drug therapy is hampered by poor access of most drugs to the brain due to the insurmountable blood-brain barrier (BBB). Nanotechnology holds great promise for noninvasive therapy of severe brain diseases. Furthermore, recent bioconjugation strategies have enabled the invasion of the BBB via tailored-designed bioconjugates either with targeting moieties or alterations in the physicochemical and/or the pharmacokinetic parameters of central nervous system (CNS) active pharmaceutical ingredients. Multifunctional systems and new entities are being developed to target brain cells and tumor cells to resist the progression of brain tumors. Direct conjugation of an FDA-approved drug with a targeting moiety, diagnostic moiety, or pharmacokinetic-modifying moiety represents another current approach in combating brain tumors and metastases. Finally, genetic engineering, stem cells, and vaccinations are innovative nontraditional approaches described in different patents for the management of brain tumors and metastases. This review summarizes the recent technologies and patent applications in the past five years for the noninvasive treatment of glioblastoma and other brain tumors. Till now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are ongoing to bring novel CNS delivery systems to potential clinical application.

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Pharmacokinetics, Brain Delivery, and Efficacy in Brain Tumor-Bearing Mice of Glutathione Pegylated Liposomal Doxorubicin (2B3-101)

Cited by 230 publications

References 46 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

Managing CNS Tumors: The Nanomedicine Approach

Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

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