scholarly journals SCIDOT-35. A NOVEL MODEL FOR THE OPTIMIZATION OF DRUG-DEVICE COMBINATIONS FOR THE TREATMENT OF BRAIN TUMORS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi279-vi279
Author(s):  
Clare Killick-Cole ◽  
Max Woolley ◽  
David Johnson ◽  
Owen Lewis ◽  
Patrick Moore ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Drug Delivery System ◽  
Delivery System ◽  
Treatment Strategies ◽  
Clinical Translation ◽  
Preclinical Model ◽  
Preclinical Models ◽  
Convection Enhanced Delivery ◽  
Head Fixation

Abstract BACKGROUND Failure of many brain tumor treatments has been attributed to the inability of a compound to cross the blood-brain barrier. Convection-enhanced delivery (CED) offers a method to administer drugs directly to the tumor site, thereby mitigating this limitation. CED has been used in several preclinical and clinical studies, though an approved treatment is yet to come to fruition. A medical device suitable for repeated intraparenchymal delivery is valuable for brain tumor treatment strategies, but a lack of appropriate preclinical models capable of infusing clinically relevant volumes has hindered progress in clinical translation. Currently utilized preclinical models include porcine, which have limited use due to their growth rates and canine and non-human primates, which are restricted by ethical considerations. This study investigates the functional characteristics and stability of the Renishaw clinical Neuroinfuse™ drug delivery system in an ovine model. METHODS A head fixation frame was refined for ovine stereotactic surgery. Eight Romney ewes were implanted with the drug delivery system, comprising of four catheters and a transcutaneous port allowing chronic re-access infusions without repeated surgery. A maximum of four infusions were performed per subject, at four to eight-week intervals. RESULTS The implantation of the Neuroinfuse™ drug delivery system was well-tolerated in all subjects, without serious device related adverse events. Artificial CSF/gadolinium infusions were performed on five subjects. Three subjects were maintained for a follow-up study. Putaminal and thalamic distribution volumes remained stable over the re-access period of up to six months post-implantation. CONCLUSION Romney ewes are suitable for the stereotactic implantation of the Neuroinfuse™ chronic drug delivery system. Transcutaneous ports remained integrated for the study duration, allowing repeated intraparenchymal delivery. This novel preclinical model provides a stable platform for infusion regime optimization of drug-device combinations for chronic CED, which will undoubtably de-risk clinical translation in the neuro-oncology CED field.

scholarly journals Two-Step Targeted Drug Delivery Via Proteinaceous Barnase-Barstar Interface and PLGA-Based Nano-Carrier

2021 ◽  
Author(s):  
Victoria O. Shipunova ◽  
Elena N. Komedchikova ◽  
Anna S. Sogomonyan ◽  
Polina A. Kotelnikova ◽  
Maxim P. Nikitin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Drug Delivery System ◽  
Delivery System ◽  
Nile Blue ◽  
Treatment Strategies ◽  
Systemic Toxicity ◽  
Blue Dye ◽  
Two Stage

Abstract The conventional methods of treating cancer with chemo- and radiotherapy present plenty of serious problems, such as low therapeutic index and high systemic toxicity. The advanced cancer treatment strategies utilize nanoformulations of drugs that can enter a tumor due to the enhanced permeability and retention (EPR) effect. However, EPR fails in the treatment of several human diseases. Mainstream biomedical studies are focused on creating the drugs that would enter the tumor with higher effectiveness and require smaller doses for administration. A two-stage drug delivery system is an encouraging alternative solution. At first, the primary, non-toxic targeting module is delivered to the tumor cells, followed by injection of the second complementary targeting module at a considerably lower dose, thus decreasing systemic toxicity. To meet the challenge, we have developed a two-stage drug delivery system (DDS), mediated by the high-affinity binding of the Barnase*Barstar protein pair. Barnase and Barstar act as lego bricks linking the first and the second modules on the surface of the cancer cell. Barnase (12 kDa) is a natural ribonuclease from Bacillus amyloliquefaciens, while Barstar (10 kDa) is its natural inhibitor. The Barnase*Barstar is one of the strongest known protein*protein complexes with Kaff = 1014 M−1 exhibiting extraordinarily stability in severe conditions. Artificial scaffold polypeptide DARPin9_29 genetically fused with Barstar served is a first module of the developed two-step DDS. DARPin9_29 (14 kDa) specifically recognizes the tumor marker HER2 overexpressed on human breast cancer cells. As a second module, a therapeutic nano-cargo was developed based on fluorescent polymer PLGA nanoparticles loaded with diagnostic Nile Blue dye and the chemotherapeutic drug doxorubicin. This nano-PLGA structure was covalently coupled to Barnase. We showed two-stage efficient labeling of HER2-overexpressing cancer cells using the first non-toxic module DARPin9_29-Barstar and the second toxic nano-module PLGA-Barnase. We demonstrated the doxorubicin-induced cytotoxicity of this two-step DDS based on polymer nanoparticles and proteinaceous Barnase-Barstar interface and showed more than 10-fold therapeutic dose reduction versus free doxorubicin. We believe that the developed two-step DDS based on PLGA nano-cargo and protein interface will promote the creation of new-generation cancer treatment strategies.

scholarly journals Specificity of brain tumor capillaries and novel drug delivery system

1997 ◽  
Vol 6 (1) ◽  
pp. 39-44
Author(s):  
Kiyonobu Ikezaki ◽  
Takanori Inamura ◽  
Ken Samoto ◽  
Koichiro Matsukado ◽  
Tadahisa Shono ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Drug Delivery System ◽  
Delivery System ◽  
Novel Drug Delivery System ◽  
Novel Drug

Coloring brain tumor with multi-potent micellar nanoscale drug delivery system

2012 ◽  
Author(s):  
Kyuha Chong ◽  
Kyungsun Choi ◽  
EunSoo Kim ◽  
Eun Chun Han ◽  
Jungsul Lee ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Drug Delivery System ◽  
Delivery System

scholarly journals New drug delivery system for brain tumor chemotherapy using 40.DEG.C.-adriamycin thermosensitive liposome.

1996 ◽  
Vol 11 (5) ◽  
pp. 351-354 ◽  
Author(s):  
Kenichi Kakinuma ◽  
Ryuichi Tanaka ◽  
Masashi Kato ◽  
Hideaki Takahashi ◽  
Tsuyoshi Suda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Drug Delivery System ◽  
Delivery System ◽  
New Drug ◽  
Thermosensitive Liposome ◽  
Brain Tumor Chemotherapy

scholarly journals Modern Developments of Nano Based Drug Delivery System by Combined with Phytochemicals- Presenting New Aspects

2021 ◽  
pp. 107-129
Author(s):  
Ranajit Nath ◽  
Ratna Roy ◽  
Gourav Barai ◽  
Shishir Bairagi ◽  
Supratip Manna ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Combined Treatment ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Advantages And Disadvantages ◽  
Therapeutic Drugs ◽  
Anti Cancer ◽  
Current Scenario

Nanomedicine are a relatively new but quickly expanding discipline in which tiny materials are used as diagnostic instruments or to administer therapeutic drugs to particular targets in a controlled manner. Nanotechnology provides a number of advantages in the treatment of chronic human diseases by allowing precise medications to be delivered to particular locations. There have been several notable uses of nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents, etc.) in the treatment of various illnesses in recent years. Neverthless, In current scenario there are phytochemicals are also present whom are responsible for prevention of devastating diseases. In this review it has been highlighted that there are real possible outcomes present, in the case of the combined treatment strategies of phytochemicals and nanoparticles. Eventually, this combined drug delivery system play crucial role in anti-cancer, anti-alzehimar, anti-bacterial and many more complicated maladies. We also focused on the preclinical and clinical study regarding the drug delivery system. Here, the types of phytochemicals along with their bioavilability also mentioned. Additionally, the Nanomedicines' advantages and disadvantages in drug delivery from synthetic to natural sources to clinical applications are also explored. In addition, we've added information about nanomedicine's developments by attaching with phytochemicals with respect to the diseases and future prospects.

Hexosomes based on cholesterol and phosphatidylcholine: a new drug delivery system for curcumin release

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
AR Bilia ◽  
G Capecchi ◽  
MC Salvatici ◽  
B Isacchi ◽  
MC Bergonzi
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
New Drug
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