(2021) In Vitro Apoptosis Evaluation and Kinetic Modeling onto Cyclodextrin-Based Host–Guest Magnetic Nanoparticles Containing Methotrexate and Tamoxifen. BioNanoScience. pp. 667-677. ISSN 21911630 (ISSN)
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Abstract
Supramolecular carriers as a targeted drug delivery system have a significant role in managing the pharmacokinetics and pharmacodynamics of drugs. Therefore, in this project, we used cyclodextrin (CD) as a host molecule for tamoxifen (TMX) and methotrexate (MTX) to evaluate apoptosis mechanism and statistical patterns of release. The flow cytometry analysis showed that combination therapy by anticancer drugs was successful in apoptosis induction compared to free TMX and MTX. Also, real-time PCR and western blot analyses were performed to measure gene expression of Bak1, Bclx, and caspase-3 in estrogen and folate receptor-positive MCF-7 cell lines. All results confirmed that MNPs containing TMX and MTX can significantly increase Bak1/Bclx ratios plus the activity of caspase-3, while free MTX and free TMX showed no effects on triggering apoptosis after 24 h of exposure. According to results of pharmacokinetic studies onto TMX and MTX release, it is revealed that both models that consist of Sahlin-Peppas and Ritger-Peppas create the good fitting curves more than other statistical patterns at both low and high temperatures (37°C and 42°C). For this reason, activation parameters (ΔH‡, ΔS‡, and ΔG‡) were calculated to estimate the favorable model. The lower energy barrier indicates that the Sahlin-Peppas is the favorable model with both diffusion and relaxation process. Therefore, combination therapy by two anticancer drugs, TMX and MTX, utilizing cyclodextrin-based host–guest supramolecular magnetic nanoparticles (CD-MNPs) provided new results for induction of apoptosis and pharmacokinetic model. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
| Item Type: | Article |
|---|---|
| Keywords: | Apoptosis Flow cytometry Gene expression Mathematical models of drug release Supramolecular magnetic nanoparticles Cell culture Cell death Controlled drug delivery Curve fitting Cyclodextrins Magnetic nanoparticles Pharmacokinetics Polymerase chain reaction Supramolecular chemistry Activation parameter Flow cytometry analysis Lower energy barriers Pharmacokinetic model Pharmacokinetic studies Pharmacokinetics and pharmacodynamics Targeted drug delivery systems Western-blot analysis Targeted drug delivery beta actin caspase 3 cyclodextrin magnetic nanoparticle methotrexate methotrexate and tamoxifen cyclodextrin based host guest magnetic nanoparticle protein Bax protein bcl 2 protein bcl x tamoxifen unclassified drug Article Bak1 gene breast cancer cell line chemoluminescence controlled study down regulation drug activity drug delivery system drug formulation drug release enzyme activity gene human human cell in vitro study kinetics mathematical model MTT assay oxidative stress particle size pharmacodynamics protein expression protein function radioimmunoprecipitation real time polymerase chain reaction software upregulation Western blotting |
| Divisions: | |
| Page Range: | pp. 667-677 |
| Journal or Publication Title: | BioNanoScience |
| Volume: | 11 |
| Number: | 3 |
| Identification Number: | 10.1007/s12668-021-00877-8 |
| ISSN: | 21911630 (ISSN) |
| Depositing User: | مهندس مهدی شریفی |
| URI: | http://eprints.zbmu.ac.ir/id/eprint/4018 |
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