Preclinical therapeutic efficacy of a novel blood-brain barrier-penetrant dual PI3K/mTOR inhibitor with preferential response in PI3K/PTEN mutant glioma

Here we present the first pyrimido-pyrrolo-oxazine-based mTOR kinase inhibitor (11) predicted to penetrate the blood brain barrier (BBB). Thus, 11 has a potential in treatments of neurological disorders.

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Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood-brain barrier modification in glioblastoma

Neurosurgery ◽

10.1097/00006123-198610000-00011 ◽

1986 ◽

Vol 19 (4) ◽

pp. 573???82 ◽

Cited By ~ 11

Author(s):

E A Neuwelt ◽

J Howieson ◽

E P Frenkel ◽

H D Specht ◽

R Weigel ◽

...

Keyword(s):

Drug Delivery ◽

Blood Brain Barrier ◽

Therapeutic Efficacy ◽

Brain Barrier ◽

Blood Brain ◽

Multiagent Chemotherapy

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The blood-brain barrier limits the therapeutic efficacy of antibody drug conjugates in glioblastoma

Neuro-Oncology ◽

10.1093/neuonc/noab223 ◽

2021 ◽

Author(s):

Roger Abounader ◽

David Schiff

Keyword(s):

Blood Brain Barrier ◽

Therapeutic Efficacy ◽

Brain Barrier ◽

Antibody Drug Conjugates ◽

Drug Conjugates ◽

Blood Brain ◽

Antibody Drug

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Novel Drug Delivery System for Curcumin: Implementation to Improve Therapeutic Efficacy against Neurological Disorders

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210705114058 ◽

2021 ◽

Vol 24 ◽

Author(s):

Roohi Mohi-ud-din ◽

Reyaz Hassan Mir ◽

Taha Umair Wani ◽

Abdul Jalil Shah ◽

Ishtiyaq Mohi-Ud-Din ◽

...

Keyword(s):

Blood Brain Barrier ◽

Therapeutic Efficacy ◽

Therapeutic Potential ◽

Polymeric Nanoparticles ◽

Curcuma Longa ◽

Brain Barrier ◽

Barrier Methods ◽

Blood Brain ◽

Toxicological Studies ◽

Novel Drug

Background: Curcumin, a hydrophobic polyphenolic compound present in Curcuma longa Linn. (Turmeric), has been used to improve various neurodegenerative conditions, including Amyotrophic lateral sclerosis, Multiple Sclerosis, Parkinson's disease, Prion disease, stroke, anxiety, depression, and ageing. However, the blood-brain barrier (BBB) impedes the delivery of curcumin to the brain, as a result, limits its therapeutic potential. Objective/Aim: This review summarises the recent advances towards the therapeutic efficacy of curcumin along with various novel strategies to overcome its poor bioavailability across the blood-brain barrier. Methods: The collection of data for the compilation of this review work was searched in PubMed Scopus, Google Scholar, and Science Direct. Result: Various approaches have been opted to expedite the delivery of curcumin across the blood-brain barrier, including liposomes, micelles, polymeric nanoparticles, exosomes, dual targeting Nanoparticles etc. Conclusion: The review also summarises the numerous toxicological studies and the role of curcumin in CNS disorders.

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Y1 receptor ligand-based nanomicelle as a novel nanoprobe for glioma-targeted imaging and therapy

Nanoscale ◽

10.1039/c8nr00148k ◽

2018 ◽

Vol 10 (13) ◽

pp. 5845-5851 ◽

Cited By ~ 4

Author(s):

Juan Li ◽

Yang Du ◽

Zhenqi Jiang ◽

Yuchen Tian ◽

Nianxiang Qiu ◽

...

Keyword(s):

Blood Brain Barrier ◽

Therapeutic Efficacy ◽

Brain Barrier ◽

Targeted Imaging ◽

Receptor Ligand ◽

Y1 Receptor ◽

Blood Brain

Y1 receptor ligand AP-NPY facilitates circumvention of the blood brain barrier by nanomicelles specifically targeting glioma, improving therapeutic efficacy and prolonging survival.

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Quantifying glioblastoma drug response dynamics incorporating resistance and blood brain barrier penetrance from experimental data

10.1101/822585 ◽

2019 ◽

Author(s):

Susan Christine Massey ◽

Javier C. Urcuyo ◽

Bianca Maria Marin ◽

Jann N. Sarkaria ◽

Kristin R. Swanson

Keyword(s):

Experimental Data ◽

Mathematical Model ◽

Blood Brain Barrier ◽

Therapeutic Efficacy ◽

Drug Response ◽

Treated Patient ◽

Brain Barrier ◽

Imaging Data ◽

Response Dynamics ◽

Blood Brain

AbstractMany drugs investigated for the treatment of glioblastoma (GBM) have had poor clinical outcomes, as their efficacy is dependent on adequate delivery to sensitive tumor cell populations, which is limited by the blood-brain barrier (BBB). Further complicating evaluation of therapeutic efficacy, tumors can become resistant to anti-cancer drugs, and it can be difficult to gauge the extent to which BBB limitations and resistance each contribute to a drug’s failure. To address this question, we developed a minimal mathematical model to characterize these elements of overall drug response, informed by time-series bioluminescence imaging data from a treated patient-derived xenograft (PDX) experimental model. By fitting this mathematical model to a preliminary dataset in a series of nonlinear regression steps, we estimated parameter values for individual PDX subjects that correspond to the dynamics seen in experimental data. Using these estimates, we performed a parameter sensitivity analysis using Latin hypercube sampling and partial rank correlation coefficients. Results from this analysis combined with simulation results suggest that BBB permeability may play a slightly larger role in therapeutic efficacy than drug resistance. Our model and fitting technique to estimate parameters from data may be a useful tool in aiding further exploration of these challenges in future studies of drug efficacy with larger datasets.

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