Automated Analysis of Polyethylene Glycol-Induced Inhibition of P-Glycoprotein Activity In Vitro

2003 ◽  
Vol 92 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Erin D. Hugger ◽  
Clayton J. Cole ◽  
Thomas J. Raub ◽  
Philip S. Burton ◽  
Ronald T. Borchardt
Keyword(s):  
Polyethylene Glycol ◽  
Automated Analysis ◽  
P Glycoprotein

scholarly journals Modified Gold Nanoparticles for Efficient Delivery of Betulinic Acid to Cancer Cell Mitochondria

2021 ◽  
Vol 22 (10) ◽  
pp. 5072
Author(s):  
Olakunle Oladimeji ◽  
Jude Akinyelu ◽  
Aliscia Daniels ◽  
Moganavelli Singh
Keyword(s):  
Polyethylene Glycol ◽  
Cancer Cell ◽  
Betulinic Acid ◽  
Targeted Delivery ◽  
Epigallocatechin Gallate ◽  
High Amplitude ◽  
Significant Inhibition ◽  
Mitochondrial Targeting ◽  
The Impact

Advances in nanomedicine have seen the adaptation of nanoparticles (NPs) for subcellular delivery for enhanced therapeutic impact and reduced side effects. The pivotal role of the mitochondria in apoptosis and their potential as a target in cancers enables selective induction of cancer cell death. In this study, we examined the mitochondrial targeted delivery of betulinic acid (BA) by the mitochondriotropic TPP+-functionalized epigallocatechin gallate (EGCG)-capped gold NPs (AuNPs), comparing the impact of polyethylene glycol (PEG) and poly-L-lysine-graft-polyethylene glycol (PLL-g-PEG) copolymer on delivery efficacy. This included the assessment of their cellular uptake, mitochondrial localization and efficacy as therapeutic delivery platforms for BA in the human Caco-2, HeLa and MCF-7 cancer cell lines. These mitochondrial-targeted nanocomplexes demonstrated significant inhibition of cancer cell growth, with targeted nanocomplexes recording IC50 values in the range of 3.12–13.2 µM compared to that of the free BA (9.74–36.31 µM) in vitro, demonstrating the merit of mitochondrial targeting. Their mechanisms of action implicated high amplitude mitochondrial depolarization, caspases 3/7 activation, with an associated arrest at the G0/G1 phase of the cell cycle. This nano-delivery system is a potentially viable platform for mitochondrial-targeted delivery of BA and highlights mitochondrial targeting as an option in cancer therapy.

scholarly journals Mesoporous Properties of Bioactive Glass Synthesized by Spray Pyrolysis with Various Polyethylene Glycol and Acid Additions

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 618
Author(s):  
Tzu-Yu Peng ◽  
Pei-Yun Tsai ◽  
May-Show Chen ◽  
Yuichi Mine ◽  
Shan-Hua Wu ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Polyethylene Glycol ◽  
Bioactive Glass ◽  
Spray Pyrolysis ◽  
Mesoporous Structure ◽  
High Specific Surface Area ◽  
Process Time ◽  
In Vitro Bioactivity ◽  
One Pot

Mesoporous bioactive glass (MBG) has a high specific surface area, promoting the reaction area, thereby improving the bioactivity; thus, MBG is currently gaining popularity in the biomaterial field. Spray pyrolysis (SP) is a one-pot process that has the advantages of shorter process time and better particle bioactivity, therefore, MBG was prepared by SP process with various polyethylene glycol (PEG, molecular weight ranged from 2000–12,000) and acid (HCl and CH3COOH) additions. In vitro bioactivity and mesoporous properties of the so-obtained MBG were investigated. The experimental results showed that all the MBG exhibited amorphous and mesoporous structure. Increasing the molecular weight of PEG can improve the mesoporous structure and bioactivity of MBG. Whereas optimized MBG was prepared with suitable concentration of PEG and CH3COOH. In the present work, MBG synthesized via spray pyrolysis by adding 5 g of PEG with a molecular weight of 12,000 and 50 mL of CH3COOH exhibited the best in vitro bioactivity and mesoporous structure.

scholarly journals Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal absorption of octreotide in rats with portal hypertension

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoyu Sun ◽  
Shunxiong Tang ◽  
Binbin Hou ◽  
Zhijun Duan ◽  
Zhen Liu ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Western Blot ◽  
In Vitro Experiments ◽  
Rt Pcr ◽  
P Glycoprotein ◽  
Intestinal Microsomes ◽  
First Pass

Abstract Background Portal hypertension (PH) is the main cause of complications and death in liver cirrhosis. The effect of oral administration of octreotide (OCT), a drug that reduces PH by the constriction of mesenteric arteries, is limited by a remarkable intestinal first-pass elimination. Methods The bile duct ligation (BDL) was used in rats to induce liver cirrhosis with PH to examine the kinetics and molecular factors such as P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and cytochrome P450 3A4 (CYP3A4) influencing the intestinal OCT absorption via in situ and in vitro experiments on jejunal segments, transportation experiments on Caco-2 cells and experiments using intestinal microsomes and recombinant human CYP3A4. Moreover, RT-PCR, western blot, and immunohistochemistry were performed. Results Both in situ and in vitro experiments in jejunal segments showed that intestinal OCT absorption in both control and PH rats was largely controlled by P-gp and, to a lesser extent, by MRP2. OCT transport mediated by P-gp and MRP2 was demonstrated on Caco-2 cells. The results of RT-PCR, western blot, and immunohistochemistry suggested that impaired OCT absorption in PH was in part due to the jejunal upregulation of these two transporters. The use of intestinal microsomes and recombinant human CYP3A4 revealed that CYP3A4 metabolized OCT, and its upregulation in PH likely contributed to impaired drug absorption. Conclusions Inhibition of P-gp, MRP2, and CYP3A4 might represent a valid option for decreasing intestinal first-pass effects on orally administered OCT, thereby increasing its bioavailability to alleviate PH in patients with cirrhosis.

scholarly journals Overcoming multidrug-resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416

2012 ◽  
Vol 32 (6) ◽  
pp. 559-566 ◽  
Author(s):  
Yan Xu ◽  
Feng Zhi ◽  
Guangming Xu ◽  
Xiaolei Tang ◽  
Sheng Lu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Chemotherapy ◽  
Antitumour Activity ◽  
Multidrug Resistant ◽  
The Novel ◽  
Mice Model ◽  
P Glycoprotein ◽  
Channel Currents

MDR (multidrug-resistance) represents a major obstacle to successful cancer chemotherapy and is usually accomplished by overexpression of P-gp (P-glycoprotein). Much effort has been devoted to developing P-gp inhibitors to modulate MDR. However, none of the inhibitors on the market have been successful. 1416 [1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (phenoprolamine hydrochloride)] is a new VER (verapamil) analogue with a higher IC50 for blocking calcium channel currents than VER. In the present paper, we examined the inhibition effect of 1416 on P-gp both in vitro and in vivo. 1416 significantly enhanced cytotoxicity of VBL (vinblastine) in P-gp-overexpressed human multidrug-resistant K562/ADM (adriamycin) and KBV cells, but had no such effect on the parent K562 and KB cells. The MDR-modulating function of 1416 was further confirmed by increasing intracellular Rh123 (rhodanmine123) content in MDR cells. Human K562/ADM xenograft-nude mice model verified that 1416 potentiates the antitumour activity of VBL in vivo. RT-PCR (reverse transcriptase-PCR) and FACS analysis demonstrated that the expression of MDR1/P-gp was not affected by 1416 treatment. All these observations suggest that 1416 could be a promising agent for overcoming MDR in cancer chemotherapy.

Triterpenoid Saponins from the Caryophyllaceae Family Modulate the Efflux Activity of the P-Glycoprotein in an In Vitro Model of Intestinal Barrier

Planta Medica ◽  
2016 ◽  
Vol 82 (18) ◽  
pp. 1553-1557 ◽  
Author(s):  
Océane Dubray ◽  
Brice Moulari ◽  
Claire Chrétien ◽  
Yann Pellequer ◽  
Alf Lamprecht ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Intestinal Barrier ◽  
Triterpenoid Saponins ◽  
P Glycoprotein ◽  
Vitro Model

In Vitro and in Vivo Evaluation of Phenylbutenoid Dimers as Inhibitors of P-Glycoprotein

2013 ◽  
Vol 76 (12) ◽  
pp. 2277-2281 ◽  
Author(s):  
Song Wha Chae ◽  
Ah-Reum Han ◽  
Jung Hyun Park ◽  
Jeong Yeon Rhie ◽  
Hee-Jong Lim ◽  
...  
Keyword(s):  
In Vivo Evaluation ◽  
P Glycoprotein

scholarly journals P-Glycoprotein and Breast Cancer Resistance Protein Restrict Apical-to-Basolateral Permeability of Human Brain Endothelium to Amyloid-β

2009 ◽  
Vol 29 (6) ◽  
pp. 1079-1083 ◽  
Author(s):  
Leon M Tai ◽  
A Jane Loughlin ◽  
David K Male ◽  
Ignacio A Romero
Keyword(s):  
Breast Cancer ◽  
Human Brain ◽  
Breast Cancer Resistance Protein ◽  
Amyloid Β ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Resistance Protein ◽  
The Brain

The clearance of amyloid beta (Aβ) from the brain represents a novel therapeutic target for Alzheimer's disease. Conflicting data exist regarding the contribution of adenosine triphosphatebinding cassette transporters to the clearance of Aβ through the blood-brain barrier. Therefore, we investigated whether Aβ could be a substrate for P-glycoprotein (P-gp) and/or for breast cancer resistance protein (BCRP) using a human brain endothelial cell line, hCMEC/D3. Inhibition of P-gp and BCRP increased apical-to-basolateral, but not basolateral-to-apical, permeability of hCMEC/D3 cells to 125l Aβ 1–40. Our in vitro data suggest that P-gp and BCRP might act to prevent the blood-borne Aβ 1–40 from entering the brain.

Sign in / Sign up

Export Citation Format

Share Document