Novel Drug Delivery Strategies in Neuro-Oncology

Bidros, Dani S.; Vogelbaum, Michael A.

doi:10.1016/j.nurt.2009.04.004

Cited by 101 publications

(86 citation statements)

References 46 publications

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“…104,110 Compared with traditional delivery methods, CED has shown its unique characteristics for CNS delivery. 111 Without molecular weight limitation, CED can provide effective drug concentration in the region of structure into which the catheter is placed (Table 3). Furthermore, CED within the defined infusion measurements does not produce cerebral edema or measurable increases in intracranial pressure.…”

Section: Convection-enhanced Delivery (Ced)mentioning

confidence: 99%

Current approaches to enhance CNS delivery of drugs across the brain barriers

Lu¹,

Zhao²,

Wong³

et al. 2014

IJN

269

168

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Although many agents have therapeutic potentials for central nervous system (CNS) diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed.

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Section: Convection-enhanced Delivery (Ced)mentioning

confidence: 99%

Current approaches to enhance CNS delivery of drugs across the brain barriers

Lu¹,

Zhao²,

Wong³

et al. 2014

IJN

269

168

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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%

“…To overcome limited diffusion and drug dosage, research has looked at convection enhanced delivery (CED) [5,19,21,22]. Using a pumping device connected to a stereotactically implanted catheter, a drug solution is pressure driven into the cavity.…”

Section: Intracerebral Drug Delivery Strategies For Glioma Treatmentmentioning

confidence: 99%

“…However, a degree of backflow is common in CED due to the pressure necessary to pump the fluid, up to 70 mmHg [19]. This backflow could cause the drug to spread too much and lead to chemical meningitis and neurotoxicity [5,19,22]. Other drawbacks include invasiveness, long infusion times, and high intracranial pressure.…”

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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“…Overexpression and aberrant splicing of APP that results in abnormal deposits of insoluble Aβ peptide is considered to be the major incentive for the pathological changes of AD. 37,38 The toxic Aβ fragment, amyloid-β 1-42 , exerts neurotoxicity on rat hippocampal neurons in primary culture. 31 Directly injecting amyloid-β 1-42 into the hippocampus of rats can induce characteristic pathological changes of AD.…”

mentioning

confidence: 99%

A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β<sub>1–42</sub>-injected mice

Jia¹,

Sun²,

Lu³

et al. 2016

IJN

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Due to the impermeability of the blood–brain barrier and the nonselective distribution of drugs in the brain, the therapeutic access to intractable neurological disorders is challenging. In this study, dual brain-targeting polymersomes (POs) functionalized by transferrin and Tet-1 peptide (Tf/Tet-1-POs) promoted the transportation of curcumin into the brain and provided neuroprotection. The modification of the ligands that bind to the surface of POs was revealed by X-ray photoelectron spectroscopy analysis. The cell uptake of a coculture model of mouse brain capillary endothelial cells with neurons showed that the Tf/Tet-1-POs had significant transportation properties and possessed affinity for neurons. The pharmacokinetic analysis showed that the blood–brain barrier permeability–surface efficiency of the Tf/Tet-1-POs was 0.28 mL/h/g and that the brain tissue uptake rate (% ID/g) was 0.08, which were significant compared with the controls ( P <0.05). The curcumin-encapsulated Tf/Tet-1-POs provided neuroprotection and ameliorated cognitive dysfunction in intrahippocampal amyloid-β 1–42 -injected mice. These results suggest that the dual brain-targeting POs are more capable of drug delivery to the brain that can be exploited as a multiple noninvasive vehicle for targeting therapeutics.

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Novel Drug Delivery Strategies in Neuro-Oncology

Cited by 101 publications

References 46 publications

Current approaches to enhance CNS delivery of drugs across the brain barriers

Current approaches to enhance CNS delivery of drugs across the brain barriers

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β<sub>1–42</sub>-injected mice

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Novel Drug Delivery Strategies in Neuro-Oncology

Cited by 101 publications

References 46 publications

Current approaches to enhance CNS delivery of drugs across the brain barriers

Current approaches to enhance CNS delivery of drugs across the brain barriers

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-&beta;<sub>1&ndash;42</sub>-injected mice

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A dual brain-targeting curcumin-loaded polymersomes ameliorated cognitive dysfunction in intrahippocampal amyloid-β<sub>1–42</sub>-injected mice