The Use of Anthracyclines for Therapy of CNS Tumors

Ros, Martina Da; Iorio, Anna Lisa; Lucchesi, M; Stival, Alessia; Martino, Maurizio de; Sardi, Iacopo

doi:10.2174/1871520615666150407155319

Cited by 27 publications

(15 citation statements)

References 81 publications

(100 reference statements)

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“…doxorubicin, are the class of antitumor drugs with the most extensive spectrum of activity in clinical oncology and have been used for various types of tumours, including brain neoplasms such as neuroblastoma etc. However, their ability to penetrate the BBB is poor when administered intravenously due to multidrug resistance, which greatly inhibits the cytotoxic dose given to lesions in the brain (Ros et al 2015). Bypassing the P-glycoprotein drug efflux transporter, that plays a vital role in multidrug resistance mechanisms in the brain, is crucial in order to deliver drugs across the BBB for treatment of brain neoplasms through non-invasive strategies.…”

Section: Rationale For Thesismentioning

confidence: 99%

“…The thesis's work focuses on drug loading and release for glioblastoma multiforme (GBM) treatment, in a sustained and controlled manner, by polymeric microcarriers that have been specifically designed for their role. The drug of choice, doxorubicin, has a wide-ranging spectrum of activity in cancer therapeutics and has been used for treatment of brain neoplasms, although cannot effectively pass through the blood-brain barrier (BBB) due to multidrug resistance (Ros et al 2015).…”

Section: Doxorubicin Release Studymentioning

confidence: 99%

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Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

Azhar¹

2019

Preprint

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Poly(ethylene glycol) diacrylate (PEGDA)-based cryogel microcarriers incorporated with variable proportion of 3-Sulpho-propyl acrylate (SPA) were synthesized to deliver the broad-spectrum anticancer drug, doxorubicin, in a controlled and sustained method across the blood-brain barrier (BBB) for treatment of glioblastoma multiforme (GBM). Combination of these two polymeric materials was intended to allow the delivery of doxorubicin molecules through the brain parenchyma without prompting multidrug resistance mechanism by the BBB. Due to it its binding affinity to protonated doxorubicin molecules, molar percentage of incorporated SPA into the cryogel microcarriers was hypothesized to be proportional to the level of doxorubicin uptake. To enable droplet formation, fluorinated oil with perfluoropolyether surfactant served as the continuous phase. The prepolymer droplets were fabricated using a T-junction microfluidic device and were crosslinked via photopolymerization. Light microscopy was used for characterization of the microcarriers before and after cryogelation, with regards to size and shape. Doxorubicin loading and release studies were performed to evaluate drug elution rates for each type of microcarrier suspension. Loading of cryogel microcarriers was done at room temperature for a period of 7 days whereas the release study was carried out at 37°C in an incubator for 28 days. Significant differences (p < 0.0001) in uptake and release of doxorubicin, compared to the control, were seen in all SPA incorporated cryogels while those cryogels without any proportion of SPA incorporation had no significant difference ( p > 0.05). Cryogel suspensions with a SPA to PEGDA molar percentage of 60% or less were coherent with the proposed hypothesis, however, microcarriers that had a higher proportion of SPA did not seem to follow this trend. In conclusion, doxorubicin loading and release in cryogel microcarriers is not entirely dependent on its binding affinity with available SPA functional groups, but also on other physiological and mechanical parameters as well.

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Section: Rationale For Thesismentioning

confidence: 99%

Section: Doxorubicin Release Studymentioning

confidence: 99%

Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

Azhar¹

2019

Preprint

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“…The BBB, comprised of endothelial efflux transporters as well as brain endothelial cells with tight junctions between them, regulates the extravasation of molecules and cells into and out of the central nervous system (CNS) (8). Merely to quote a few examples, anthracyclines show potent effects in inhibiting cell growth in many types of tumors but they suffer from a poor penetration into the brain when intravenously administered (45). Merely to quote a few examples, anthracyclines show potent effects in inhibiting cell growth in many types of tumors but they suffer from a poor penetration into the brain when intravenously administered (45).…”

Section: High Grade Gliomas: Twice As Difficultmentioning

confidence: 99%

“…While metabolic substrates like carbohydrates and aminoacids are able to traverse the BBB by specific carrier-mediated transport systems like glucose transporters present on both the luminal and abluminal side of the BBB (46) many therapeutics such as mostly available cytotoxic drugs that are large hydrophobic molecules or antibody-based proteins, have limited permeability and do not cross the BBB (4). Merely to quote a few examples, anthracyclines show potent effects in inhibiting cell growth in many types of tumors but they suffer from a poor penetration into the brain when intravenously administered (45). The in vivo efficacy of MK-1775, a specific inhibitor of the nuclear kinase Wee1 that regulates key DNA damage checkpoints, is limited by poor delivery to the tumor: MK-1775 is ineffective when combined with temozolomide (TMZ) in treatment of brain tumors, whereas in a flank model of HGG, MK-1775 exhibits both single-agent and combinatorial activity with TMZ (44).…”

Section: High Grade Gliomas: Twice As Difficultmentioning

confidence: 99%

Advances in drug delivery to high grade gliomas

Fròsina

2016

Brain Pathology

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If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor barriers and reach adequate concentrations at the tumor sites. Effective delivery of drugs to brain cancer tissues is thus a necessary, albeit not sufficient, condition to effectively target the disease. In order to analyze the current status of research on drug delivery to high grade gliomas (HGG-WHO grades III and IV), the most frequent and aggressive brain cancers, a literature search was conducted in PubMed using the terms: "drug delivery and brain tumor" over the publication year 2015. Currently explored drug delivery techniques for HGG include the convection and permeabilization-enhanced deliveries, drug-releasing depots and Ommaya reservoirs. The efficacy/safety ratio widely varies among these techniques and the success of current efforts to increase this ratio widely varies as well.

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“…The four major anthracyclines that are used for cancer treatment are doxorubicin, daunorubicin, epirubicin, and idarubicin [6]. Among the various types of anthracyclines, doxorubicin is the most commonly administered drug [7]. N-acetylcysteine is an important drug that is used to treat acetaminophen overdose [8].…”

Section: Introductionmentioning

confidence: 99%

The Effect of N-Acetylcysteine Administration to Prevent Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients

Khazdooz

Nourian

Jalaeikhoo

et al. 2019

Multidiscip Cancer Investig

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Introduction: Anthracyclines are one of the classes of chemotherapy drugs that are widely used to treat many types of cancers including breast cancer. Taking this class of medications has a significant relationship with cardiac dysfunction. N-acetylcysteine has antioxidant properties and may be effective in preventing cardiac dysfunctions. In this study, we investigated the effect of N-acetylcysteine in preventing cardiotoxicity in breast cancer patients receiving anthracycline. Methods: A total of 60 breast cancer patients who underwent chemotherapy with anthracyclines were enrolled in the present case-control study and divided into two groups. The case group received 600 mg of N-acetylcysteine per day adjacent to chemotherapy; while the control group did not receive this medication. One month after the last chemotherapy session, troponin I was measured as a predictor of cardiotoxicity. Results: Troponin I was positive in one patient in the case group compared with 3 patients in the control group without any significant difference among groups (P> 0.05) However, the respective mean±SD level of troponin I was 0.120±0.039 and 0.192±0.063 in the case and control groups with a statistically significant difference among groups (P <0.001). Conclusions: Administration of 600 mg N-acetylcysteine per day during the anthracyclinebased chemotherapy protocol in breast cancer patients may reduce the mean troponin I levels which can be a prediction of reduced anthracyclines cardiotoxicity.

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The Use of Anthracyclines for Therapy of CNS Tumors

Cited by 27 publications

References 81 publications

Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

Advances in drug delivery to high grade gliomas

The Effect of N-Acetylcysteine Administration to Prevent Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients

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