The inhibition of interaction with serum albumin enhances the physiological activity of curcumin by increasing its cellular uptake.

2022 ◽  
Author(s):  
Mayuko Itaya ◽  
Taiki Miyazawa ◽  
Saoussane Khalifa ◽  
Naoki Shimizu ◽  
Kiyotaka Nakagawa
Keyword(s):  
Serum Albumin ◽  
Cellular Uptake ◽  
Physiological Activity ◽  
Free Drug

Based on the free drug hypothesis, we hypothesized that food compounds that bind stronger to BSA than CUR inhibit the binding between BSA and CUR, and that this results in...

scholarly journals Optimization and Evaluation of Poly(lactide-co-glycolide) Nanoparticles for Enhanced Cellular Uptake and Efficacy of Paclitaxel in the Treatment of Head and Neck Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 828
Author(s):  
Mohamed Haider ◽  
Amr Elsherbeny ◽  
Jayalakshmi Jagal ◽  
Anna Hubatová-Vacková ◽  
Iman Saad Ahmed
Keyword(s):  
Cellular Uptake ◽  
Fold Increase ◽  
Systemic Circulation ◽  
Free Drug ◽  
Carcinoma Cells ◽  
Spherical Particles ◽  
In Vitro Drug Release ◽  
Formulation Parameters ◽  
Drug Solution

The particle size (PS) and encapsulation efficiency (EE%) of drug-loaded nanoparticles (NPs) may inhibit their cellular uptake and lead to possible leakage of the drug into the systemic circulation at the tumor site. In this work, ultra-high paclitaxel-loaded poly(lactide-co-glycolide) NPs (PTX-PLGA-NPs) with ultra-small sizes were prepared and optimized by adopting the principles of quality by design (QbD) approach. The optimized PTX-PLGA-NPs showed ultra-small spherical particles of about 53 nm with EE% exceeding 90%, a relatively low polydispersity index (PDI) of 0.221, an effective surface charge of −10.1 mV, and a 10-fold increase in the in vitro drug release over 72 h relative to free drug. The cellular viability of pharynx carcinoma cells decreased by almost 50% in 24 h following treatment with optimized PTX-PLGA-NPs, compared to only 20% from the free drug. The intracellular uptake of PTX-PLGA-NPs was highly favored, and the antitumor activity of PTX was remarkably improved with a reduction in its half maximal inhibitory concentration (IC50), by almost 50% relative to free drug solution. These results suggest that the optimal critical formulation parameters, guided by QbD principles, could produce PLGA-NPs with remarkably high EE% and ultra-small PS, resulting in enhanced cellular uptake and efficacy of PTX.

N-acetylcysteine delivery with silica nanoparticles into 3T3-L1 adipocytes

2021 ◽  
Author(s):  
Evelyn Frontera ◽  
Martin F Desimone ◽  
Mauricio C De Marzi ◽  
Liliana N Guerra
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Silica Nanoparticles ◽  
Cellular Uptake ◽  
Bovine Serum ◽  
Cytotoxic Effect ◽  
Cellular Accumulation ◽  
Dose Dependent

Background: The addition of 5 mM N-acetylcysteine (NAC) to 3T3-L1 adipocytes culture inhibits the accumulation of triglycerides (Tg) by 50%, but after 48 h uptake was only 16% of total NAC available. Based on these results, the aim of this study is to increase the NAC cellular uptake by encapsulating it in silica nanoparticles (NPs). Materials & methods: Silica NPs, 20 ± 4.5 nm in size, were developed, with an inner cavity loaded with 5 mM NAC. At 48 h after treatment, there was a dose-dependent cytotoxic effect. We attempted to reduce the cytotoxicity of silica NPs by coating them with bovine serum albumin. Results: While we obtained nontoxic bovine serum albumin coated NPs, their effect on Tg cellular accumulation was also reduced.

scholarly journals Metabolism of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) and lyso-PAF (1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine) by cultured rat Kupffer cells

1989 ◽  
Vol 261 (1) ◽  
pp. 77-81 ◽  
Author(s):  
W Chao ◽  
A Siafaka-Kapadai ◽  
D J Hanahan ◽  
M S Olson
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Cellular Uptake ◽  
Kupffer Cells ◽  
Bovine Serum ◽  
Platelet Activating Factor ◽  
Metabolic Product ◽  
Supernatant Fraction ◽  
Substantial Influence ◽  
Subsequent Formation

The metabolism of platelet-activating factor (PAF; identified as AGEPC: 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) and lyso-PAF (lyso-GEPC: 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine) was investigated in cultured rat Kupffer cells. The rat Kupffer cells accumulated [3H]AGEPC and deacetylated this compound to the corresponding [3H]lyso-GEPC, which was the major metabolic product of [3H]AGEPC. [3H]Lyso-GEPC was distributed primarily in the supernatant fraction of incubated cells throughout the experimental interval. Only a very small portion of the [3H]lyso-GEPC was further converted to 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC), indicating that this acylation process was not particularly active in these cells. When [3H]lyso-GEPC was incubated with Kupffer cells, the conversion of lyso-GEPC to AGEPC via the acetyltransferase reaction increased up to 30 min and declined thereafter. Bovine serum albumin (BSA) had a substantial influence on both the cellular uptake and the metabolism of [3H]AGEPC. An increase in the BSA concentration in the incubation media reduced the cellular uptake of [3H]AGEPC and the subsequent formation of lyso-GEPC. The results of this study suggest that the hepatic Kupffer cells play an important role in the metabolism of PAF. Moreover, these results infer that the regulation of the PAF level in certain hepatic pathophysiological situations may be a consequence of the production and subsequent metabolism of this potent lipid autacoid in the Kupffer cells of the liver.

scholarly journals Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 224
Author(s):  
Saranya Chaiwaree ◽  
Ausanai Prapan ◽  
Nittiya Suwannasom ◽  
Tomás Laporte ◽  
Tanja Neumann ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Cellular Uptake ◽  
In Vitro Release ◽  
Submicron Particles ◽  
Antibiotic Drug

Doxorubicin (DOX) is an effective anthracycline antibiotic drug which is commonly used in a broad range cancer therapy. However, due to dose depending side effects and toxicity to non-cancerous tissues, its clinical applications are restricted. To overcome these limitations, human serum albumin (HSA) has been investigated as a biocompatible drug delivery vehicle. In this study, human serum albumin submicron particles (HSA-MPs) were fabricated by using the Co-precipitation–Crosslinking–Dissolution technique (CCD technique) and DOX was loaded into the protein particles by absorption. DOX-HSA-MPs showed uniform peanut-like shape, submicron size and negative zeta-potential (−13 mV). The DOX entrapment efficiency was 25% of the initial amount. The in vitro release in phosphate buffered saline pH 7.4 was less than 1% within 5 h. In contrast, up to 40% of the entrapped DOX was released in presence of a protein digesting enzyme mixture (Pronase®) within the same time. In addition, in vitro cytotoxicity and cellular uptake of DOX-HSA-MPs were evaluated using the lung carcinoma cell line A549. The results demonstrated that DOX-HSA-MPs reduced the cell metabolic activities after 72 h. Interestingly, DOX-HSA-MPs were taken up by A549 cells up to 98% and localized in the cell lysosomal compartment. This study suggests that DOX-HSA-MPs which was fabricated by CCD technique is seen as a promising biopolymer particle as well as a viable alternative for drug delivery application to use for cancer therapy.

Cellular uptake mechanisms and responses to NO transferred from mono- and poly-S-nitrosated human serum albumin

2011 ◽  
Vol 45 (10) ◽  
pp. 1196-1206 ◽  
Author(s):  
Yu Ishima ◽  
Fumika Yoshida ◽  
Ulrich Kragh-Hansen ◽  
Kaori Watanabe ◽  
Naohisa Katayama ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Cellular Uptake ◽  
Uptake Mechanisms

Use of the overturn end point in goldfish to measure the interaction of diazepam and ethanol and the effects of the binding of diazepam to bovine serum albumin

1979 ◽  
Vol 57 (10) ◽  
pp. 1186-1188 ◽  
Author(s):  
H. G. Giles ◽  
G. Kadar ◽  
S. M. MacLeod ◽  
E. M. Sellers
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Aqueous Solutions ◽  
Bovine Serum ◽  
Free Drug ◽  
End Point ◽  
Drug Concentrations ◽  
Ethanol Addition

Over the ranges 2.8 × 10−6 to 8.78 × 10−5 M diazepam and 4.85 × 10−2 to 1.22 × 10−1 M ethanol, addition of the effects of these agents on the overturn end point in goldfish was observed. The addition of bovine serum albumin (1.56 × 10−5 M) to aqueous solutions of diazepam modifies the diazepam effect by reducing the "free" drug concentrations.

Cytotoxicity of Methotrexate Conjugated to Glycerol Phosphate Modified Superparamagnetic Iron Oxide Nanoparticles

2021 ◽  
Vol 21 (3) ◽  
pp. 1451-1461
Author(s):  
Daiana K. Deda ◽  
Roberta M. Cardoso ◽  
Rodrigo K. Kawassaki ◽  
André R. de Oliveira ◽  
Sergio H. Toma ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Cellular Uptake ◽  
Cancer Cell Line ◽  
Superparamagnetic Iron Oxide ◽  
Free Drug ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Glycerol Phosphate ◽  
Mcf 7

A systematic study was carried out to evaluate the uptake and cytotoxicity of methotrexate (MTX) conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) modified with glycerol phosphate (Glyc) and phosphorylethanolamine (PEA), using MCF-7 cancer cell line as model. The ligand shell composition was controlled in such a way to get SPIONs with nine different surface functionalization and up to three co-conjugated ligands but the very iron oxide core, in order to test and compare uptake and cytotoxicity, and verify possible additive effects. Folic acid (FA), the non-toxic analogue of MTX, was also explored as ligand for SPIONs. Glyc was shown to enhance dramatically the cellular uptake despite the high negative zeta potentials, whereas PEA, FA and MTX was found to have a much lower effect on the cellular uptake. Also, a significant ten times lowering of IC50 was observed for the co-conjugated MTX in the SPION-Glyc/PEA/MTX as compared to the free drug, whereas the analogue SPION-Glyc/PEA/FA nanoparticles exhibited no significant cytotoxicity. In short, the conjugation of MTX to SPIONs enhanced dramatically its cytotoxicity and decreased the IC50 value against MCF-7 tumor cells as compared to the free drug, probably due to the enhanced uptake of SPIONs as a result of their surface modification with Glyc/PEA, demonstrating that SPION-Glyc/PEA is a good nanocarrier for co-conjugated methotrexate.

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