The blood-brain and blood-tumor barriers: A review of strategies for increasing drug delivery

Groothuis, Dennis R.

doi:10.1215/15228517-2-1-45

Cited by 95 publications

(95 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By initiating angiogenesis, the tumor can induce the host's microvasculature to undergo sprouting, thereby effectively supporting the tumor ability to invade the surrounding parenchyma [32]. It is evident from the result of this study that the tumor vasculature is lar [33].…”

Section: Discussionmentioning

confidence: 57%

Detection of T2 changes in an early mouse brain tumor

Błasiak

Tomanek

Abulrob

et al. 2010

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 57%

Detection of T2 changes in an early mouse brain tumor

Błasiak

Tomanek

Abulrob

et al. 2010

Magnetic Resonance Imaging

View full text Add to dashboard Cite

“…This is due to a number of reasons including limitations imposed by the bloodbrain-barrier (BBB) and blood-tumor-barrier (BTB), difficulties in systemic drug dosing and delivery, tumor cell uptake, intrinsic tumor resistance, and the heterogeneous cell makeup of human gliomas. In recent years much effort has been placed on trying to improve and increase drug delivery to the central nervous system (CNS) [17,38]. Intravascular strategies such as chemical modifications of drugs that allow passage across the BBB and BTB, intra-arterial therapy with BBB disruption, and receptor-mediated transport have all proved promising but are associated with significant systemic toxicity and have poorly defined intrathecal pharmacokinetics [17].…”

Section: Discussionmentioning

confidence: 99%

“…In recent years much effort has been placed on trying to improve and increase drug delivery to the central nervous system (CNS) [17,38]. Intravascular strategies such as chemical modifications of drugs that allow passage across the BBB and BTB, intra-arterial therapy with BBB disruption, and receptor-mediated transport have all proved promising but are associated with significant systemic toxicity and have poorly defined intrathecal pharmacokinetics [17]. Injection or infusion of anti-cancer agents directly into the brain or its cavities is an alternative strategy that has gained widespread popularity.…”

Section: Discussionmentioning

confidence: 99%

Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

et al. 2006

View full text Add to dashboard Cite

Docetaxel (Taxotere ® ) is a hemisynthetic, anti-cancer compound with good preclinical and clinical activity in a variety of systemic neoplasms. We tested its activity against malignant gliomas using local delivery methods. Antitumor activity was assessed in vitro against human and rat brain-tumor cell lines. For in vivo evaluation, we incorporated docetaxel into a biodegradable polymer matrix, determined associated toxicity in the rat brain, and measured efficacy at extending survival in a rat model of malignant glioma. Also, we examined the combined local delivery of docetaxel with carmustine (BCNU) against the experimental intracranial glioma. Rats bearing intracranial 9L gliosarcomas were treated 5 days after tumor implantation with various polymers (placebo, 5% docetaxel, 3.8% BCNU, or 5% docetaxel and 3.8% BCNU combination). Animals receiving docetaxel polymers (n = 15, median survival 39.1 days) had significantly improved survival over control animals (n = 12, median survival 22.5 days, P = 0.01). Similarly, animals receiving BCNU polymers (n = 15, median survival 39.3 days, 13.3% long-term survivors) demonstrated an increase in survival compared to the controls (P = 0.04). Animals receiving the combination polymers demonstrated a modest increase in survival compared to either chemotherapeutic agent alone (n = 14, median survival 54.9 days, 28.6% long-term survivors) with markedly improved survival over controls (P = 0.003). We conclude that locally delivered docetaxel shows promise as a novel antiglioma therapy and that the combination of drug regimens via biodegradable polymers may be a great therapeutic benefit to patients with malignant glioma.

show abstract

“…The bleak survival rate is attributed to such factors as tumor drug resistance, intracellular drug metabolism, and limited drug uptake, in part due to the major obstacle of the blood brain barrier, and tumor regrowth [12][13][14][15]. For example, consider the current gold standard of care for GBMs, which includes the application of Gliadel® wafers after tumor excision.…”

Section: Limitations Of Current Therapiesmentioning

confidence: 99%

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

View full text Add to dashboard Cite

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

show abstract

The blood-brain and blood-tumor barriers: A review of strategies for increasing drug delivery

Cited by 95 publications

References 0 publications

Detection of T2 changes in an early mouse brain tumor

Detection of T2 changes in an early mouse brain tumor

Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Contact Info

Product

Resources

About