Drug delivery strategies for the treatment of malignant gliomas

Allhenn, Daniela; Boushehri, Maryam A. Shetab; Lamprecht, Alf

doi:10.1016/j.ijpharm.2012.06.025

Cited by 88 publications

(76 citation statements)

References 126 publications

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“…Reprinted from Journal of Controlled Release, 159/1, Wolinsky et al, Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers, [14][15][16][17][18][19][20][21][22][23][24][25][26]2012, with permission from Elsevier.…”

Section: Figure 11mentioning

confidence: 99%

“…These include manual injections, convection-enhanced delivery, implantable reservoirs, and biodegradable drug carriers [5,[18][19][20][21]. While the manual injection of chemotherapeutics to the cavity site is a simplistic approach, high risks of infections, edema, and backflow limits it use today, especially with less invasive and more effective technique available [5,21].…”

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

“…The Ommaya reservoir is a subcutaneous reservoir connected to a catheter that is connected to the tumor bed through the skull [5,21]. By manually compressing the reservoir, chemotherapeutics are delivered through the catheter to the tumor bed.…”

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

“…By manually compressing the reservoir, chemotherapeutics are delivered through the catheter to the tumor bed. The risk of infection and the inconvenience of having to refill the reservoir limits the wide scale clinical application of this drug delivery device [21].…”

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

“…Biodegradable drug carriers such as the Gliadel® wafers have garnered much interest from the scientific community due to their lack of systemic side effects, localized controlled drug release, minimal complexity, and full biodegradation [19][20][21]. These carriers also include gels, microcarriers, and nanocarriers [21].…”

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

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Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

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Departments of Bioengineering and Chemical EngineeringThe grim prognosis for patients diagnosed with malignant gliomas necessitates the development of new therapeutic strategies for localized and sustained drug delivery to combat tumor drug resistance and regrowth. Here we introduced the novel formulation of drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy (DREAM BIG Therapy) that is applied post-resection. DREAM BIG Therapy consists of three types of microspheres [poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and poly(ε-caprolactone) (PCL)] containing various encapsulated chemotherapeutics, suspended in a degradable, aqueous poly(Nisopropylacrylamide) (PNIPAM) solution. The thermoresponsive PNIPAM solution is capable of suspending drug encapsulated microspheres at room temperature which can be "sprayed on" the post-surgical site. The physiological temperature of the treatment site (37°C) would cause PNIPAM solution to solidify and form an adherent gel layer with entrapped microspheres, providing intimate contact with remaining tumor cells. Over time, PLGA (rapid degradation), PLA (medium speed degradation), and then PCL (slow degradation) microspheres would break iv down, releasing their drug payloads in a sequential, multi-drug release directly to the tumor site, addressing cancerous regrowth and tumor drug resistance. This dissertation will address the development of DREAM BIG Therapy, from microsphere formulation to pilot in vivo studies.Initial work focused on developing blank and drug encapsulated microspheres using emulsion techniques. Preliminary studies utilized rhodamine B as a model drug for encapsulation in PLGA, PLA, and PCL particles and optimized formulation parameters to achieve a high encapsulation. Then, gefitinib, IgG, and lomustine were encapsulated in PLGA, PLA, and PCL microspheres, respectively, achieving encapsulation efficiencies greater than 80% and drug loadings greater than 0.3%. The in vitro release of gefitinib and IgG were also studied. Gefitinib released from PLGA microspheres over 40 days while the release of IgG from PLA microspheres was slower, over a year long period.The microsphere-PNIPAM system was tested for aerosolized application ex vivo. The aqueous PNIPAM solution suspended the microspheres and was aerosolized before phase transitioning to an adherent gel layer on the tissue, entrapping the microspheres on the tissue surface. Finally, when tested in vivo, the gefitinib encapsulated PLGA microspheres entrapped in PNIPAM slowed the tumor volume growth of a subcutaneous C6 glioma in comparison to blank PLGA microspheres entrapped in PNIPAM. Overall, this research confirms the potential of DREAM BIG therapy for future use with multiple chemotherapeutics and microsphere types to combat gliomas at a localized site.v

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Section: Figure 11mentioning

confidence: 99%

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

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Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

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Lipid‐Based Nanocarriers for The Treatment of Glioblastoma

Iturrioz-Rodríguez

Bertorelli

Ciofani

2020

Advanced NanoBiomed Research

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Glioblastoma multiforme (GBM) is the most common and malignant neoplasia having origin in the brain. The current treatments involve surgery, radiotherapy, and chemotherapy, being complete surgical resection the best option for the patient survival chances. However, in those cases where a complete removal is not possible, radiation and chemotherapy are applied. Herein, the main challenges of chemotherapy, and how they can be overcome with the help of nanomedicine, are approached. Natural pathways to cross the blood–brain barrier (BBB) are detailed, and different in vivo studies where these pathways are mimicked functionalizing the nanomaterial surface are shown. Later, lipid-based nanocarriers, such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, are presented. To finish, recent studies that have used lipid-based nanosystems carrying not only therapeutic agents, yet also magnetic nanoparticles, are described. Although the advantages of using these types of nanosystems are explained, including their biocompatibility, the possibility of modifying their surface to enhance the cell targeting, and their intrinsic ability of BBB crossing, it is important to mention that research in this field is still at its early stage, and extensive preclinical and clinical investigations are mandatory in the close future.

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EMP‐induced BBB‐disruption enhances drug delivery to glioma and increases treatment efficacy in rats

Zhang

et al. 2017

Bioelectromagnetics

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Chemotherapy on gliomas is not satisfactorily efficient because the presence of blood-brain barriers (BBB) leads to inadequate exposure of tumor cells to administered drugs. In order to facilitate chemotherapeutics to penetrate BBB and increase the treatment efficacy of gliomas, electromagnetic pulse (EMP) was applied and the 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU) lomustine concentration in tumor tissue, tumor size, tumor apoptosis, and side effects were measured in glioma-bearing rat model. The results showed that EMP exposure could enhance the delivery of CCNU to tumor tissue, facilitate tumor apoptosis, and inhibit tumor growth without obvious side effects. The data indicated that EMP-induced BBB disruption could enhance delivery of CCNU to glioblastoma multiforme and increase treatment efficacy in glioma-bearing rats. Bioelectromagnetics. 39:60-67, 2018. © 2017 Wiley Periodicals, Inc.

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Drug delivery strategies for the treatment of malignant gliomas

Cited by 88 publications

References 126 publications

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Lipid‐Based Nanocarriers for The Treatment of Glioblastoma

EMP‐induced BBB‐disruption enhances drug delivery to glioma and increases treatment efficacy in rats

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