scholarly journals Metabolitin-based molecular drug delivery by targeting GPR158 in glioblastoma

2021 ◽  
Author(s):  
Huashan Zhao ◽  
Wen Zhu ◽  
Jingwei Li ◽  
Jinju Lin ◽  
Xiaohua Lei ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Imaging System ◽  
Inhibitory Effect ◽  
Brain Barrier ◽  
Blood Brain ◽  
Mouse Cortex ◽  
Diagnostic Probe ◽  
Peptide Targeting

Glioblastoma multiforme (GBM) is a lethal form of intracranial tumor. One of the obstacles to treat GBM is the blood-brain barrier which limit the transportation of drugs into the tumor site. Here, based on our previous study on metabolitin (MTL) and osteocalcin, we generated a molecular drug delivery system that consisted of metabolitin and small molecules such as fluorescent dye or peptide drugs for diagnosis and treatment. And we designed a GBM diagnostic probe (MTL-ICG) and therapeutic peptide drug (MTL-NBD) that can cross the blood-brain barrier (BBB). In a NIR animal live imaging system, we found MTL-ICG can penetrate cross BBB and label the GBM site. The in vitro experiment showed that MTL-NBD had inhibitory effect on GBM cell line (U87-MG). Besides, after orthotopic transplantation of GBM into mouse cortex, treatment of MTL-NBD intravenously showed inhibition trend, which were similar with the effect of NBD, a known anti-tumor polypeptide drug. In addition, we found the GPR158, the receptor of osteocalcin, was also high expressed in grafting site. Taken together, these findings suggest that MTL is a promising cell penetrating peptide targeting GPR158 in GBM, which provide a novel delivery tool for GBM.

Glioma-targeted dual functionalized thermosensitive Ferri-liposomes for drug delivery through an in vitro blood–brain barrier

Nanoscale ◽  
2019 ◽  
Vol 11 (32) ◽  
pp. 15057-15071 ◽  
Author(s):  
Di Shi ◽  
Gujie Mi ◽  
Yan Shen ◽  
Thomas J. Webster
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Blood Brain Barrier ◽  
Electromagnetic Energy ◽  
Brain Barrier ◽  
Blood Brain ◽  
Thermosensitive Liposome

With the combination of thermosensitive liposome and an external AMF, SPIONs inside the liposome can therefore transform the electromagnetic energy to heat and trigger drug release at desired temperature.

Optimization of osmotic blood-brain barrier opening to enable intravital microscopy studies on drug delivery in mouse cortex

2020 ◽  
Vol 317 ◽  
pp. 312-321 ◽  
Author(s):  
Chengyan Chu ◽  
Anna Jablonska ◽  
Wojciech G. Lesniak ◽  
Aline M. Thomas ◽  
Xiaoyan Lan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Intravital Microscopy ◽  
Brain Barrier ◽  
Blood Brain ◽  
Mouse Cortex ◽  
Barrier Opening ◽  
Blood Brain Barrier Opening

PLA/PLGA nanoparticles for delivery of drugs across the blood-brain barrier

2013 ◽  
Vol 2 (3) ◽  
pp. 241-257 ◽  
Author(s):  
Jingyan Li ◽  
Cristina Sabliov
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Drug Carrier ◽  
Plga Nanoparticles ◽  
Brain Barrier ◽  
Poly Lactic Acid ◽  
Blood Brain

AbstractThe blood-brain barrier (BBB), which protects the central nervous system (CNS) from unnecessary substances, is a challenging obstacle in the treatment of CNS disease. Many therapeutic agents such as hydrophilic and macromolecular drugs cannot overcome the BBB. One promising solution is the employment of polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs as drug carrier. Over the past few years, significant breakthroughs have been made in developing suitable PLGA and poly (lactic acid) (PLA) NPs for drug delivery across the BBB. Recent advances on PLGA/PLA NPs enhanced neural delivery of drugs are reviewed in this paper. Both in vitro and in vivo studies are included. In these papers, enhanced cellular uptake and therapeutic efficacy of drugs delivered with modified PLGA/PLA NPs compared with free drugs or drugs delivered by unmodified PLGA/PLA NPs were shown; no significant in vitro cytotoxicity was observed for PLGA/PLA NPs. Surface modification of PLGA/PLA NPs by coating with surfactants/polymers or covalently conjugating the NPs with targeting ligands has been confirmed to enhance drug delivery across the BBB. Most unmodified PLGA NPs showed low brain uptake (<1%), which indirectly confirms the safety of PLGA/PLA NPs used for other purposes than treating CNS diseases.

scholarly journals LRP1-mediated pH-sensitive polymersomes facilitate combination therapy of glioblastoma in vitro and in vivo

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chen He ◽  
Zhiyuan Zhang ◽  
Yinan Ding ◽  
Kangli Xue ◽  
Xihui Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Blood Brain Barrier ◽  
Delivery System ◽  
Ph Sensitive ◽  
Brain Barrier ◽  
Blood Brain ◽  
Good Ability ◽  
Complex Drug

Abstract Background Glioblastoma (GBM) is the most invasive primary intracranial tumor, and its effective treatment is one of the most daunting challenges in oncology. The blood–brain barrier (BBB) is the main obstacle that prevents the delivery of potentially active therapeutic compounds. In this study, a new type of pH-sensitive polymersomes has been designed for glioblastoma therapy to achieve a combination of radiotherapy and chemotherapy for U87-MG human glioblastoma xenografts in nude mice and significantly increased survival time. Results The Au-DOX@PO-ANG has a good ability to cross the blood–brain barrier and target tumors. This delivery system has pH-sensitivity and the ability to respond to the tumor microenvironment. Gold nanoparticles and doxorubicin are designed as a complex drug. This type of complex drug improve the radiotherapy (RT) effect of glioblastoma. The mice treated with Au-DOX@PO-ANG NPs have a significant reduction in tumor volume. Conclusion In summary, a new pH-sensitive drug delivery system was fabricated for the treatment of glioblastoma. The new BBB-traversing drug delivery system potentially represents a novel approach to improve the effects of the treatment of intracranial tumors and provides hope for glioblastoma treatment.

scholarly journals LRP1-mediated pH-sensitive Polymersomes Facilitate Combination Therapy of Glioblastoma in Vitro and in Vivo

2020 ◽  
Author(s):  
Chen He ◽  
Zhiyuan Zhang ◽  
Yinan Ding ◽  
Kangli Xue ◽  
Xihui Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Blood Brain Barrier ◽  
Delivery System ◽  
Ph Sensitive ◽  
Brain Barrier ◽  
Blood Brain ◽  
Good Ability ◽  
Complex Drug

Abstract Background: Glioblastoma (GBM) is the most invasive primary intracranial tumor, and its effective treatment is one of the most daunting challenges in oncology. The blood-brain barrier (BBB) is the main obstacle that prevents the delivery of potentially active therapeutic compounds. In this study, a new type of pH-sensitive polymersomes has been designed for glioblastoma therapy to achieve a combination of radiotherapy and chemotherapy for U87-MG human glioblastoma xenografts in nude mice and significantly increased survival time.Results: The Au-DOX@PO-ANG has a good ability to cross the blood-brain barrier and target tumors. This delivery system has pH-sensitivity and the ability to respond to the tumor microenvironment. Gold nanoparticles and doxorubicin are designed as a complex drug. This type of complex drug improve the radiotherapy (RT) effect of glioblastoma. The mice treated with Au-DOX@PO-ANG NPs have a significant reduction in tumor volume.Conclusion: In summary, a new pH-sensitive drug delivery system was fabricated for the treatment of glioblastoma. The new BBB-traversing drug delivery system potentially represents a novel approach to improve the effects of the treatment of intracranial tumors and provides hope for glioblastoma treatment.

DDRE-49. TRANSIENT OPENING OF THE BLOOD-BRAIN BARRIER BY VASOACTIVE PEPTIDES TO INCREASE CNS DRUG DELIVERY: REALITY VERSUS WISHFUL THINKING?

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi85-vi85
Author(s):  
Matthew Smith-Cohn ◽  
Nicholas Burley ◽  
Stuart Grossman
Keyword(s):  
Drug Delivery ◽  
Blood Vessels ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Specific Information ◽  
Vasoactive Peptides ◽  
Cns Drug Delivery ◽  
Blood Brain ◽  
Bbb Permeability

Abstract BACKGROUND Drug delivery to treat neurologic disease and cancers of the central nervous system (CNS) is severely limited by the blood-brain barrier (BBB). Vasoactive peptides (VAPs) such as regadenoson, adenosine, and labradimil have been shown in animal studies to transiently open the BBB, and regadenoson is currently under investigation in humans to determine if it might improve CNS drug delivery. There is currently limited information regarding the potential for other VAPs to open the BBB transiently. METHODS We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the BBB, we devised a four-tier classification system to organize data available in the literature which factors in alterations in BBB integrity and effects on normal brain vasculature and systemic blood vessels. This data was further sorted based on whether it comes from humans, animals, or in vitro systems. RESULTS We identified 38 VAPs with potential BBB permeability-altering properties. To date, none of these has been shown to open the BBB in humans. Thirteen VAPs increased BBB permeability in rodents. The remaining 25 had favorable physiologic effects on blood vessels but lack specific information on permeability changes to the BBB. We ranked VAPs in a four-tier ranking system related to their known physiologic actions. CONCLUSION Rodent studies document that analogs of bradykinin and adenosine transiently disrupt the BBB leading to higher chemotherapy concentrations in the CNS. VAPs remain an understudied class of drugs with the potential to increase drug delivery to the CNS. Dozens of VAPs have yet to be formally evaluated for this important clinical effect. This retrospective review summarizes the available data on VAPs highlighting agents that deserve further in vitro and in vivo investigations.

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