Metformin-loaded nanoerythrosomes: An erythrocyte-based drug delivery system as a therapeutic tool for glioma

Glioma is an intra-cranial malignancy with the origin of neural stem cells or precursor cells, the most prevalent brain tumor worldwide. Glioblastoma, the fourth-grade glioma, is a common brain tumor whose incidence rate is 5–7 people per 100,000 populations annually. Despite their high mortality rate, all efforts for treatment have yet to achieve any desirable clinical outcome. The Wnt signaling pathway is a conserved pathway among species that seems to be a candidate for cancer therapy by its inhibition. Metformin is a known inhibitor of the Wnt signaling pathway. Its effects on glioma treatment have been observed in cellular, animal, and clinical experiments. Nanoerythrosomes are drug carriers obtained from the cellular membrane of red blood cells in nano size which can offer several characteristics to deliver metformin to brain tumors. They are good at loading and carrying hydrophilic drugs, they can protect metformin from its metabolizing enzymes, which are present in the blood-brain barrier, and they can extend the period of metformin presence in circulation. In this study, nanoerythrosomes were prepared by using the hypotonic buffer. They had particle sizes in the range of 97.1 ± 34.2 nm, and their loading efficiency and loading capacity were 72.6% and 1.66%, respectively. Nanoerythrosomes could reserve metformin in their structure for a long time, and only 50% of metformin was released after 30 h. Moreover, they released metformin at a low and approximately constant rate. Besides, nanoerythrosomes could tolerate various kinds of stress and maintain most of the drug in their structure. Altogether, nanoerythrosome can be a suitable drug delivery system to deliver therapeutic amounts of metformin to various tissues.