scholarly journals Phase I/II and Phase II Studies of Targeted Gene Delivery In Vivo: Intravenous Rexin-G for Chemotherapy-resistant Sarcoma and Osteosarcoma

2009 ◽  
Vol 17 (9) ◽  
pp. 1651-1657 ◽  
Author(s):  
Sant P Chawla ◽  
Victoria S Chua ◽  
Lita Fernandez ◽  
Doris Quon ◽  
Andreh Saralou ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Phase I ◽  
Phase Ii ◽  
Targeted Gene Delivery ◽  
Phase Ii Studies

Phase I study of NK105, a paclitaxel-incorporating micellar nanoparticle, in patients with advanced cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2018-2018 ◽  
Author(s):  
K. Kato ◽  
T. Hamaguchi ◽  
H. Yasui ◽  
T. Okusaka ◽  
H. Ueno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
Polymeric Micelle ◽  
Preclinical Study ◽  
Hematological Toxicity ◽  
Phase Ii Studies ◽  
Grade 3

2018 Background: NK105 is a new polymeric micelle carrier system for paclitaxel (PTX). A preclinical study revealed that the plasma AUC and tumor AUC of NK105 were 90-fold higher and 25-fold higher, respectively, than those of free-PTX, i.e., the conventional PTX formulation. NK105 had higher in vivo antitumor activity and lower neurotoxicity than free-PTX. This phase I study was designed to examine the MTD, DLTs, recommended dose (RD) for phase II, and the pharmacokinetics of NK105. Methods: NK105 was administered as a 1-hour intravenous infusion every 3 weeks, without antiallergic premedication. The starting dose was 10 mg PTX equivalent/m2, and the dose was escalated according to the accelerated titration method. Results: To date, 17 patients (pts) have received the following doses: 10 mg/m2 (n=1); 20 mg/m2 (n=1); 40 mg/m2 (n=1); 80 mg/m2 (n=1); 110 mg/m2 (n=3); 150 mg/m2 (n=5); and 180 mg/m2 (n=5). The tumor types treated included pancreatic (n=9), bile duct (n=5), gastric (n=2), and colonic (n=1) cancers. Neutropenia was the most common hematological toxicity. Grade 3 fever developed in 1 pt given 180 mg/m2. No other grade 3 or 4 non-hematological toxicity, including neuropathy, was observed. DLTs occurred in pts given 180 mg/m2 (grade 4 neutropenia lasting for more than 5 days). This dose was designated as the MTD. Allergic reactions developed in only one pt at 180 mg/m2, who was sensitive to other drugs such as antibiotics anti-inflammatory. A partial response was observed in one pt with pancreatic cancer and pts with colonic and gastric cancer had stable disease. The Cmax and AUC of NK105 were dose dependent. The plasma AUC of NK105 at 180 mg/m2 was approximately 30-fold higher than that of the conventional formulation of PTX. Conclusions: Accrual is ongoing at the 150 mg/m2 dose level to determine the RD. DLT was Grade 4 neutropenia. NK105 produces prolonged high levels of PTX in plasma. A 1-hour infusion of NK105 every 3 weeks was feasible, well tolerated, and effective in patients with pancreatic cancer. Even after the long term usage, only grade 1 or 2 neuropathy was observed. NK105 will be evaluated in Phase II studies of patients with advanced pancreatic and gastric cancers. No significant financial relationships to disclose.

scholarly journals Advanced Phase I/II Studies of Targeted Gene Delivery In Vivo: Intravenous Rexin-G for Gemcitabine-resistant Metastatic Pancreatic Cancer

2010 ◽  
Vol 18 (2) ◽  
pp. 435-441 ◽  
Author(s):  
Sant P Chawla ◽  
Victoria S Chua ◽  
Lita Fernandez ◽  
Dorris Quon ◽  
William C Blackwelder ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Gene Delivery ◽  
Phase I ◽  
Metastatic Pancreatic Cancer ◽  
Targeted Gene Delivery ◽  
Advanced Phase

Effects of Ofloxacin Administration on the Reliability of Urine Glucose Testing

1996 ◽  
Vol 30 (5) ◽  
pp. 469-472
Author(s):  
Tsong-Mei Tsai ◽  
Brian F Shea ◽  
Paul F Souney ◽  
Fred G Volinsky ◽  
Joseph M Scavone ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Tertiary Care ◽  
Urine Samples ◽  
Care Hospital ◽  
Open Label ◽  
Urine Glucose ◽  
Glucose Testing

OBJECTIVE: TO study the effects of ofloxacin on the reliability of urine glucose testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0–4 hours postdose, and (3) pooled 4–8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin concentrations in phase I (0,25,50, 100, 200,400, and 800 μg/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II. CONCLUSIONS: In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations. Supported by a grant from the RW Johnson Pharmaceutical Research Institute. Presented in abstract form at the American College of Clinical Pharmacy 1994 Winter Practice and Research Forum, February 6–9, 1994, San Diego. CA.

scholarly journals A supramolecular platform for controlling and optimizing molecular architectures of siRNA targeted delivery vehicles

2020 ◽  
Vol 6 (31) ◽  
pp. eabc2148
Author(s):  
Yuting Wen ◽  
Hongzhen Bai ◽  
Jingling Zhu ◽  
Xia Song ◽  
Guping Tang ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Tumor Therapy ◽  
Sirna Delivery ◽  
Targeted Gene Delivery ◽  
Delivery Vehicles ◽  
Molecular Architectures ◽  
Host Polymer

It requires multistep synthesis and conjugation processes to incorporate multifunctionalities into a polyplex gene vehicle to overcome numerous hurdles during gene delivery. Here, we describe a supramolecular platform to precisely control, screen, and optimize molecular architectures of siRNA targeted delivery vehicles, which is based on rationally designed host-guest complexation between a β-cyclodextrin–based cationic host polymer and a library of guest polymers with various PEG shape and size, and various density of ligands. The host polymer is responsible to load/unload siRNA, while the guest polymer is responsible to shield the vehicles from nonspecific cellular uptake, to prolong their circulation time, and to target tumor cells. A series of precisely controlled molecular architectures through a simple assembly process allow for a rapid optimization of siRNA delivery vehicles in vitro and in vivo for therapeutic siRNA-Bcl2 delivery and tumor therapy, indicating the platform is a powerful screening tool for targeted gene delivery vehicles.

scholarly journals Ochratoxin A-Induced Hepatotoxicity through Phase I and Phase II Reactions Regulated by AhR in Liver Cells

Toxins ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 377 ◽  
Author(s):  
Hye Soo Shin ◽  
Hyun Jung Lee ◽  
Min Cheol Pyo ◽  
Dojin Ryu ◽  
Kwang-Won Lee
Keyword(s):  
Oxidative Stress ◽  
Phase I ◽  
Ochratoxin A ◽  
Phase Ii ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Aryl Hydrocarbon ◽  
Similar Mode ◽  
Phase I And Ii

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. OTA exists in a variety of foods, including rice, oats, and coffee and is hepatotoxic, with a similar mode of action as aflatoxin B1. The precise mechanism of cytotoxicity is not yet known, but oxidative damage is suspected to contribute to its cytotoxic effects. In this study, human hepatocyte HepG2 cells were treated with various concentrations of OTA (5–500 nM) for 48 h. OTA triggered oxidative stress as demonstrated by glutathione depletion and increased reactive oxygen species, malondialdehyde level, and nitric oxide production. Apoptosis was observed with 500 nM OTA treatment. OTA increased both the mRNA and protein expression of phase I and II enzymes. The same results were observed in an in vivo study using ICR mice. Furthermore, the relationship between phase I and II enzymes was demonstrated by the knockdown of the aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) with siRNA. Taken together, our results show that OTA induces oxidative stress through the phase I reaction regulated by AhR and induces apoptosis, and that the phase II reaction is activated by Nrf2 in the presence of oxidative stress.

Receptor-Mediated Gene Delivery Using Chitosan Derivatives In Vitro and In Vivo

2007 ◽  
Vol 342-343 ◽  
pp. 449-452 ◽  
Author(s):  
Tae Hee Kim ◽  
Hua Jin ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.

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