Long-term stabilization in patients with malignant glioma after treatment with liposomal doxorubicin

Fabel, Klaus; Dietrich, Jörg; Hau, Peter; Wismeth, Caecilie; Winner, Beate; Przywara, S; Steinbrecher, Andreas; Ullrich, W.; Bogdahn, Ulrich

doi:10.1002/1097-0142(20011001)92:7<1936::aid-cncr1712>3.0.co;2-h

Cited by 137 publications

(90 citation statements)

References 28 publications

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“…267 In contrast, in a cohort of patients with brain cancer, liposomal DOX, DNR, or bleomycin was found moderately effective against glioma. 275,278,279,[281][282][283] Based on the moderate efficacy of liposomal formulations against brain tumors, it is clear that more effective drug-delivery strategies are needed. One promising alternative strategy involves the combination of ultrasound and microbubbles to induce BBB opening for local and transient delivery of drugs into the brain, leading to improvement in chemotherapy treatment.…”

Section: Design Of Liposomal Drug-delivery Systems For Glioma Therapymentioning

confidence: 99%

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Vieira

Gamarra

2016

IJN

356

238

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This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood–brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer’s, Parkinson’s, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood–brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

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Section: Design Of Liposomal Drug-delivery Systems For Glioma Therapymentioning

confidence: 99%

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Vieira

Gamarra

2016

IJN

356

238

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“…Using an animal model, researchers found that brain concentration of doxorubicin were higher by more than a log value when delivered as a nanoparticle. Fabel et al (83) treated patients with high-grade malignant gliomas with liposomal doxorubicin and found moderate activity and improved overall survival when compared with past trials using other possible therapies. Hau et al (84) used a pegylated liposomal formulation of doxorubicin in patients with recurrent high-grade glioma and also found it to be moderately effective and well tolerated.…”

Section: New Drug Class Formulations For Crossing the Bbbmentioning

confidence: 99%

The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses

Deeken

Löscher

2007

Clinical Cancer Research

626

492

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Despite scientific advances in understanding the causes and treatment of human malignancy, a persistent challenge facing basic and clinical investigators is how to adequately treat primary and metastatic brain tumors.The blood-brain barrier is a physiologic obstruction to the delivery of systemic chemotherapy to the brain parenchyma and central nervous system (CNS). A number of physiologic properties make the endothelium in the CNS distinct from the vasculature found in the periphery. Recent evidence has shown that a critical aspect of this barrier is composed of xenobiotic transporters which extrude substrates from the brain into the cerebrospinal fluid and systemic circulation. These transporters also extrude drugs and toxins if they gain entry into the cytoplasm of brain endothelial cells before they enter the brain. This review highlights the properties of the blood-brain barrier, including the location, function, and relative importance of the drug transporters that maintain this barrier. Primary and metastatic brain malignancy can compromise this barrier, allowing some access of chemotherapy treatment to reach the tumor.The responsiveness of brain tumors to systemic treatment found in past clinical research is discussed, as are possible explanations as to why CNS tumors are nonetheless able to evade therapy. Finally, strategies to overcome this barrier and better deliver chemotherapy into CNS tumors are presented.Despite the dramatic advances in understanding the molecular basis for carcinogenesis and the development of new targeting agents to treat malignancies, a critical challenge that continues to face cancer researchers is overcoming the sanctuary for primary and metastatic disease found within the central nervous system (CNS). Brain metastases occur in a significant percentage of patients with common malignancies, with 5-year cumulative incidence rates of 16% in lung cancer patients, 7% of breast cancer patients, and 5% of patients with colon cancer (1). In diseases such as melanoma, the incidence of brain metastatic disease is reported to be as high as 55% (2). Autopsy studies show that in patients who die from cancer, up to 25% of them develop brain metastases (3).The incidence of brain metastatic disease is on the rise (4). This could be due to a number of factors, including earlier brain screening for CNS disease in cancers known to spread to the brain; improved and more widely available radiological techniques such as magnetic resonance imaging; and improved therapies to treat systemic disease, which are prolonging survival and, in turn, increasing the risk of developing metastases to the brain. The irony is that as our therapies are improving clinical outcomes and prolonging survival, the incidence of CNS disease is on the rise. Furthermore, primary brain malignancies are intrinsically resistant to most chemotherapies for reasons that are poorly understood. These realities demand that we better understand, and learn how to treat, CNS malignancy.This CNS sanctuary for metastatic as well...

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“…Thus, the use of coated nanoparticles may even present better options of the treatment of human gliomas than liposomes, which so far did not provide a successful long-term therapy of glioblastomas with doxorubicin. 20 However, a direct comparison of both vehicles in the same model system has not yet been performed.…”

Section: Potential Mechanisms Of Drug Delivery To Brainmentioning

confidence: 99%

“…18,19 In addition, the application of liposome-bound doxorubicin enabled only short-term relief to glioblastoma patients. 20 Therefore, the search for more efficient carriers to transport anticancer drugs to the brain must continue.…”

mentioning

confidence: 99%

Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles

Steiniger

Kreuter

Khalansky

et al. 2004

Intl Journal of Cancer

400

214

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Glioblastomas belong to the most aggressive human cancers with short survival times. Due to the blood-brain barrier, they are mostly inaccessible to traditional chemotherapy. We have recently shown that doxorubicin bound to polysorbate-coated nanoparticles crossed the intact blood-brain barrier, thus reaching therapeutic concentrations in the brain. Here, we investigated the therapeutic potential of this formulation of doxorubicin in vivo using an animal model created by implantation of 101/8 glioblastoma tumor in rat brains. Groups of 5-8 glioblastoma-bearing rats (total n ‫؍‬ 151) were subjected to 3 cycles of 1.5-2.5 mg/kg body weight of doxorubicin in different formulations, including doxorubicin bound to polysorbate-coated nanoparticles. The animals were analyzed for survival (% median increase of survival time, Kaplan-Meier). Preliminary histology including immunocytochemistry (glial fibrillary acidic protein, ezrin, proliferation and apoptosis) was also performed. Rats treated with doxorubicin bound to polysorbate-coated nanoparticles had significantly higher survival times compared with all other groups. Over 20% of the animals in this group showed a long-term remission. Preliminary histology confirmed lower tumor sizes and lower values for proliferation and apoptosis in this group. All groups of animals treated with polysorbatecontaining formulations also had a slight inflammatory reaction to the tumor. There was no indication of neurotoxicity. Additionally, binding to nanoparticles may reduce the systemic toxicity of doxorubicin. This study showed that therapy with doxorubicin bound to nanoparticles offers a therapeutic potential for the treatment of human glioblastoma.

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Long-term stabilization in patients with malignant glioma after treatment with liposomal doxorubicin

Cited by 137 publications

References 28 publications

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses

Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles

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Long-term stabilization in patients with malignant glioma after treatment with liposomal doxorubicin

Cited by 137 publications

References 28 publications

Getting into the brain: liposome-based strategies for effective drug delivery across the blood&ndash;brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood&ndash;brain barrier

The Blood-Brain Barrier and Cancer: Transporters, Treatment, and Trojan Horses

Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles

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Product

Resources

About

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier

Getting into the brain: liposome-based strategies for effective drug delivery across the blood–brain barrier