Impact of methotrexate-loaded fattigated albumin nanoparticles and pharmaceutical excipients on real-time reactive oxygen species and cell viability in a microfluidic chip system.
Sura Saad Abdullah, Eun-Ji Kim, Jeongro Lee, Hy Dinh Nguyen, Beom-Jin Lee
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引用次数: 0
Abstract
This study examined the impact of methotrexate (MTX)-loaded albumin-oleic acid nanoparticles (MTX-AONs) and pharmaceutical excipients (PEs) on cell viability and real-time reactive oxygen species (ROS) sensing in breast cancer cells (MCF-7) and human non-tumorigenic breast epithelial cells (MCF-10A). Water-soluble PEs, such as sodium dodecyl sulfate (SLS), D-α-tocopheryl polyethylene glycol 1000 succinate (D-α-TPGS), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), and sodium oleate (SO), were also screened for their ability to improve MTX solubility and influence cellular responses. The self-assembled albumin-oleic acid nanoparticles (AONs) prepared by desolvation, exhibited a mean particle size of 184 ± 2 nm, polydispersity index (PDI) of 0.23 ± 0.01, and zeta potential of -37.07 ± 0.9. MTX loading yielded an encapsulation efficiency of 93 % and loading of 9.3 %, increasing particle size greatly to 306.8 ± 2 nm with minimal changes in PDI (0.15 ± 0.01) and zeta potential (-30.3 ± 0.6). The PEs (1 %, w/w) influenced aqueous MTX solubility (mg/mL), giving in the order: SO (5.89 ± 0.12), SLS (1.52 ± 0.11), HP-β-CD (0.97 ± 0.03) and D-α-TPGS (0.64 ± 0.03) compared with free MTX (0.58 ± 0.04 mg/mL). Under dynamic shear stress, MTX-AONs exhibited enhanced anticancer activity compared with static conditions. Furthermore, MCF-7 cell viability was decreased in a dose-dependent manner, while MCF-10A cells were spared, suggesting better cellular uptake than that of free MTX. Co-treatment with PEs decreases MCF-7 cell viability; however, their effectiveness is not affected by MTX solubility. For example, SLS and D-α-TPGS combined with MTX-AONs showed the strongest effects on the cellular viability of MCF-7 cells in both static and dynamic environments, while maintaining MCF-10A cells. As the drug concentration increased, cell viability decreased accordingly, whereas real-time ROS production increased, indicating a good correlation. Interestingly, the expected lethal dose (LD50) calculated from the half-maximal inhibitory concentration (IC50) correlated with the reported LD50 of MTX. The microfluidic chip system can be utilized to screen the impact of formulation design and PEs in cancer therapy by simultaneously measuring cellular viability and real-time ROS levels to predict clinical relevance.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.