In Vitro Apoptosis Evaluation and Kinetic Modeling onto Cyclodextrin-Based Host–Guest Magnetic Nanoparticles Containing Methotrexate and Tamoxifen

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.