Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Upadhyay, Urvashi; Tyler, Betty; Patta, Yoda Rante; Wicks, Robert T.; Spencer, Kevin C.; Scott, Alexander W.; Masi, Byron C.; Hwang, Lee; Grossman, Rachel; Cima, Michael J.; Brem, Henry; Langer, Robert

doi:10.1073/pnas.1313420110

Cited by 21 publications

(12 citation statements)

References 28 publications

(41 reference statements)

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“…In recent years, attempts have been made to deliver chemotherapy drugs simultaneously through various delivery systems, such as micelles, liposomes, microcapsule, and inorganic NPs. 25 For example, codelivery of Dox and curcumin in poly(d,llactide-co-glycolide) NPs has been demonstrated to be an …”

Section: Characterization Of Thio-dox-loaded Mpeg-pla Npsmentioning

confidence: 99%

Codelivery of thioridazine and doxorubicin using nanoparticles for effective breast cancer therapy

Jin¹,

Zou²,

Luo³

et al. 2016

IJN

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Cancer chemotherapy can benefit from the combination of different anticancer drugs. Here, we prepared doxorubicin (Dox)- and thioridazine (Thio)-coloaded methoxy poly(ethylene glycol)-poly( l -lactic acid) (MPEG-PLA) nanoparticles (NPs) for breast cancer therapy. These NPs have an average particle size of 27 nm. The drug loading efficiencies of Thio and Dox are 4.71% and 1.98%, respectively. Compared to the treatment of Thio or Dox alone, the combination of Thio and Dox exhibited a synergistic effect in inhibiting the growth of 4T1 breast cancer cells in vitro. In addition, the Thio- and Dox-coloaded MPEG-PLA NPs could efficiently suppress the growth of breast cancer cells in vivo. This study suggests that Thio- and Dox-coloaded MPEG-PLA NPs might have potential applications in breast cancer treatment.

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Section: Characterization Of Thio-dox-loaded Mpeg-pla Npsmentioning

confidence: 99%

Codelivery of thioridazine and doxorubicin using nanoparticles for effective breast cancer therapy

Jin¹,

Zou²,

Luo³

et al. 2016

IJN

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“…Conventional chemotherapies through the intravenous delivery are oftentimes unsuccesful since the blood–brain barrier blocks delivery of drugs to brain tumors 4 . Several researches have improved controlled and targeted drug delivery to brain tumors 5–7 . For example, the biodegradable polymeric wafer 8,9 (Gliadel wafer, Arbor Pharmaceuticals, USA) implanted near the brain surgery site locally delivers drugs to remaining brain tumors and exhibits meaningful improvement.…”

Section: Introductionmentioning

confidence: 99%

Flexible, sticky, and biodegradable wireless device for drug delivery to brain tumors

et al. 2019

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Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.

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“…For intracranial chemotherapy, the BBB problematic could even be avoided because the drug is directly applied to the tumor cavity during tumor resection [ 58 , 59 ]. As has been well described in the literature for the study of GBM in vivo [ 60 , 61 , 62 , 63 ], we suggest a xenograft approach of human tumor stem cell models in rodent carriers, ideally in immune-tolerant models [ 64 ], to investigate the immune relevance of the applied intervention using nanocarried-CB839 in the future. Such an immunocompetent mouse model for human GBM cells—which has also been recently used for testing additional disease types [ 65 ]—would also help to study the effects of Au-CB839 NPs on the immune microenvironment of the tumor.…”

Section: Resultsmentioning

confidence: 99%

Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery

et al. 2021

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Gold nanoparticles (Au NPs) are studied as delivery systems to enhance the effect of the glutaminase1 inhibitor CB839, a promising drug candidate already in clinical trials for tumor treatments. Au NPs were synthesized using a bottom-up approach and covered with polymers able to bind CB839 as a Au-polymer-CB839 conjugate. The drug loading efficiency (DLE) was determined using high-performance liquid chromatography and characterization of the CB839-loaded NPs was done with various microscopic and spectroscopic methods. Despite the chemical inertness of CB839, Au NPs were efficient carriers with a DLE of up to 12%, depending on the polymer used. The therapeutic effect of CB839 with and without Au was assessed in vitro in 2D and 3D glioblastoma (GBM) cell models using different assays based on the colony formation ability of GBM stem cells (GSCs). To avoid readout disturbances from the Au metal, viability methods which do not require optical detection were hereby optimized. These showed that Au NP delivery increased the efficacy of CB839 in GSCs, compared to CB839 alone. Fluorescent microscopy proved successful NP penetration into the GSCs. With this first attempt to combine CB839 with Au nanotechnology, we hope to overcome delivery hurdles of this pharmacotherapy and increase bioavailability in target sites.

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Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Cited by 21 publications

References 28 publications

Codelivery of thioridazine and doxorubicin using nanoparticles for effective breast cancer therapy

Codelivery of thioridazine and doxorubicin using nanoparticles for effective breast cancer therapy

Flexible, sticky, and biodegradable wireless device for drug delivery to brain tumors

Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery

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