Customizing a Tridomain TRAIL Variant to Achieve Active Tumor Homing and Endogenous Albumin-Controlled Release of the Molecular Machine In Vivo

2020 ◽  
Vol 21 (10) ◽  
pp. 4017-4029
Author(s):  
Ze Tao ◽  
Yuehua Liu ◽  
Hao Yang ◽  
Yanru Feng ◽  
Heng Li ◽  
...  
Keyword(s):  
Controlled Release ◽  
Molecular Machine ◽  
Tumor Homing ◽  
Endogenous Albumin

scholarly journals Real‐Time In Vivo Detection of Cellular Senescence through the Controlled Release of the NIR Fluorescent Dye Nile Blue

2020 ◽  
Vol 59 (35) ◽  
pp. 15152-15156 ◽  
Author(s):  
Beatriz Lozano‐Torres ◽  
Juan F. Blandez ◽  
Irene Galiana ◽  
Alba García‐Fernández ◽  
María Alfonso ◽  
...  
Keyword(s):  
Controlled Release ◽  
Real Time ◽  
Cellular Senescence ◽  
Nile Blue ◽  
Fluorescent Dye ◽  
In Vivo Detection

scholarly journals EXTH-07. TUMOR-HOMING INDUCED NEURAL STEM CELLS SECRETING A CYTOTOXIC PAYLOAD AS AN ADJUVANT TREATMENT FOR NON-SMALL CELL LUNG CANCER BRAIN METASTASES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii88-ii88
Author(s):  
Alison Mercer-Smith ◽  
Wulin Jiang ◽  
Alain Valdivia ◽  
Juli Bago ◽  
Scott Floyd ◽  
...  
Keyword(s):  
Stem Cells ◽  
Brain Metastases ◽  
Neural Stem Cells ◽  
Adjuvant Treatment ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Homing ◽  
Induced Neural Stem Cells

Abstract INTRODUCTION Non-small cell lung cancer (NSCLC) is the most common cancer to form brain metastases. Radiation treatment is standard-of-care, but recurrence is still observed in 40% of patients. An adjuvant treatment is desperately needed to track down and kill tumor remnants after radiation. Tumoritropic neural stem cells (NSCs) that can home to and deliver a cytotoxic payload offer potential as such an adjuvant treatment. Here we show the transdifferentiation of human fibroblasts into tumor-homing induced neural stem cells (hiNSCs) that secrete the cytotoxic protein TRAIL (hiNSC-TRAIL) and explore the use of hiNSC-TRAIL to treat NSCLC brain metastases. METHODS To determine the migratory capacity of hiNSCs, hiNSCs were infused intracerebroventricularly (ICV) into mice bearing established bilateral NSCLC H460 brain tumors. hiNSC accumulation at tumor foci was monitored using bioluminescent imaging and post-mortem fluorescent analysis. To determine synergistic effects of radiation with TRAIL on NSCLC, we performed in vitro co-culture assays and isobologram analysis. In vivo, efficacy was determined by tracking the progression and survival of mice bearing intracranial H460 treated with hiNSC-TRAIL alone or in combination with 2 Gy radiation. RESULTS/CONCLUSION Following ICV infusion, hiNSCs persisted in the brain for > 1 week and migrated from the ventricles to colocalize with bilateral tumor foci. In vitro, viability assays and isobologram analysis revealed the combination treatment of hiNSC-TRAIL and 2 Gy radiation induced synergistic killing (combination index=0.64). In vivo, hiNSC-TRAIL/radiation combination therapy reduced tumor volumes > 90% compared to control-treated animals while radiation-only and hiNSC-TRAIL-only treated mice showed 21% and 52% reduced volumes, respectively. Dual-treatment extended survival 40%, increasing survival from a median of 20 days in controls to 28 days in the treatment group. These results suggest hiNSC-TRAIL can improve radiation therapy for NSCLC brain metastases and could potentially improve outcomes for patients suffering from this aggressive form of cancer.

Combination of hybrid peptide with biodegradable gelatin hydrogel for controlled release and enhancement of anti-tumor activity in vivo

2014 ◽  
Vol 176 ◽  
pp. 1-7 ◽  
Author(s):  
Arong Gaowa ◽  
Tomohisa Horibe ◽  
Masayuki Kohno ◽  
Keisuke Sato ◽  
Hiroshi Harada ◽  
...  
Keyword(s):  
Controlled Release ◽  
Hybrid Peptide ◽  
Gelatin Hydrogel ◽  
Anti Tumor Activity

In vivo tissue response to resorbable silica xerogels as controlled-release materials

Biomaterials ◽  
2005 ◽  
Vol 26 (9) ◽  
pp. 1043-1052 ◽  
Author(s):  
Shula Radin ◽  
Gehan El-Bassyouni ◽  
Edward J. Vresilovic ◽  
Evert Schepers ◽  
Paul Ducheyne
Keyword(s):  
Controlled Release ◽  
Tissue Response ◽  
Silica Xerogels

scholarly journals Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model

2011 ◽  
Vol 65 (1-2) ◽  
pp. 71-81
Author(s):  
Irena Homsek ◽  
Dragica Popadic ◽  
Slobodanka Simic ◽  
Slavica Ristic ◽  
Katarina Vucicevic ◽  
...  
Keyword(s):  
Controlled Release ◽  
Rabbit Model ◽  
Tablet Formulation ◽  
Human Model ◽  
In Vitro Dissolution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Drug Concentrations

Controlled-release (CR) pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ) CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC) based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans.

Development, optimization and in vivo characterization of domperidone-controlled release hot-melt-extruded films for buccal delivery

2015 ◽  
Vol 42 (3) ◽  
pp. 473-484 ◽  
Author(s):  
Chinna Reddy Palem ◽  
Narendar Reddy Dudhipala ◽  
Sunil Kumar Battu ◽  
Michael A. Repka ◽  
Madhusudan Rao Yamsani
Keyword(s):  
Controlled Release ◽  
Buccal Delivery ◽  
Extruded Films ◽  
In Vivo Characterization ◽  
Hot Melt
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