10 January 2022
Nanoparticle carriers show great promise as drug delivery systems because they can be programmed to release their load when they reach a specific location or cell type. Now, researchers at KAIMRC have designed and developed a polymer nanoparticle capable of carrying the chemotherapy drug, epirubicin, safely and directly to breast cancer cells.
Epirubicin is less cardiotoxic than its widely used derivative, doxorubicin, and has proven effective against breast, lung, and liver cancer. However, epirubicin is currently administered as an intravenous solution, and in certain cases can cause serious side effects, such as damage to DNA and cellular membranes, the formation of secondary malignancies or even extravasation - the leakage of a fluid or medicine from the vein into the surrounding area. This is largely due to the drug interfering with healthy cells and tissues en route to the tumour.
Salam Massadeh and her colleagues prepared their novel nanoparticles using three different polymers. Each nanoparticle had a hydrophobic core covered in a hydrophilic outer layer, enabling them to carry both hydrophobic and hydrophilic drugs.
The team encapsulated epirubicin in the nanoparticles. The ‘EPI-NPs’ had an encapsulation efficiency of 82% thanks to the robust synthesis method. The researchers then analysed the stability of the EPI-NPs over time and under different environmental conditions. The EPI-NPs remained stable at different pH values and retained their spherical shape throughout all trials. Crucially, they did not form aggregates – a potential stumbling block for nanoparticle drug delivery systems, which can clump together to create a blockage in a capillary. The EPI-NPs also remained stable when stored at room temperature for over 30 days.
In a series of experiments on breast cancer cell cultures, Massadeh and co-workers monitored the way in which the carrier released the drug over time. They found a strong initial release of the drug within a few hours of the nanoparticles reaching their target followed by a steady, sustained release of the drug as the EPI-NPs gradually degraded.
“Flow cytometry studies showed that the EPI-NPs have an apoptotic effect on MCF-7 breast cancer cells,” state the researchers in their paper, published in Polymers in 2021. “In addition, the high-content imaging studies revealed a gradual decrease in cancer cells number after treatment with EPI-NPs. […] Further in vivo studies are recommended as a next step to study the pharmacokinetics of the EPI-NPs in animal models.”
- Alaamery, M. et al. Development of epirubicin-loaded biocompatible polymer PLA–PEG–PLA nanoparticles: Synthesis, characterization, stability, and in vitro anticancerous assessment. Polymers 13 (1212) (2021) | article