Co-Encapsulation of Fisetin and Cisplatin into Liposomes for Glioma Therapy: From Formulation to Cell Evaluation

Abstract

(1) Background: Glioblastoma (GBM) is the most frequent cerebral tumor. It almost always relapses and there is no validated treatment for second-line GBM. We proposed the coencapsulation of fisetin and cisplatin into liposomes, aiming to (i) obtain a synergistic effect by combining the anti-angiogenic effect of fisetin with the cytotoxic effect of cisplatin, and (ii) administrate fisetin, highly insoluble in water. The design of a liposomal formulation able to encapsulate, retain and deliver both drugs appeared a challenge. (2) Methods: Liposomes with increasing ratios of cholesterol/DOPC were prepared and characterized in term of size, PDI and stability. The incorporation of fisetin was explored using DSC. The antiangiogneic and cytotoxic activities of the selected formulation were assayed in vitro. (3) Results: We successfully developed an optimized liposomal formulation incorporating both drugs, composed by DOPC/cholesterol/DODA-GLY-PEG2000 at a molar ratio of 75.3/20.8/3.9, with a diameter of 173 ± 8 nm (PDI = 0.12 ± 0.01) and a fisetin and cisplatin drug loading of 1.7 ± 0.3% and 0.8 ± 0.1%, respectively, with a relative stability over time. The maximum incorporation of fisetin into the bilayer was determined at 3.2% w/w. Then, the antiangiogenic activity of fisetin was maintained after encapsulation. The formulation showed an additive effect of cisplatin and fisetin on GBM cells; (4) Conclusions: The developed co-loaded formulation was able to retain the activity of fisetin, was effective against GBM cells and is promising for further in vivo experimentations.

Abrogation of Cellular Senescence Induced by Temozolomide in Glioblastoma Cells: Search for Senolytics

“…Three natural compounds were tested: fisetin, artesunate and curcumin. Fisetin, a polyphenol present in several fruits and vegetables and used as food supplement, has been found to be cytotoxic (at high dose) in several types of cancer, including glioma [ 49 , 50 ]. In an elegant series of experiments, it was also shown to reduce the amount of age-related senescent cells, using both in vitro and in vivo experimental systems [ 51 ].…”

“…In view of the lack of adverse effects, fisetin and artesunate might seriously be considered as adjuvant in glioma therapy. New delivery methods, such as encapsulation in lipids and micelles, are being developed to circumvent the low water solubility of fisetin and to make it useful for local administration [ 50 ]. The same holds true for artesunate, which is widely used for malaria treatment and considered safe.…”

Stimuli‐Responsive Miktoarm Polymer‐Based Formulations for Fisetin Delivery and Regulatory Effects in Hyperactive Human Microglia

“…It suggests that the thioketal unit may increase the interactions between the hydrophobic drug and the core more effectively than M3. [ 87,109 ] Fisetin‐loaded lipidoid vesicles have been shown to release more than 80% of the drug within 24 h, [ 106,108,110 ] while in those from M1 to M3 we observed 65% and 69% release from ROS and GSH‐responsive polymersomes within the same time period.…”

Identification of Immunological Characteristics and Immune Subtypes Based on Single-Sample Gene Set Enrichment Analysis Algorithm in Lower-Grade Glioma

“…Conversely, high levels of M1-type macrophages and CD8+T cells were identified as protective factors. Apart from that, the revolution of drug delivery methods in nanoplatforms and liposomes had shown a promising future to precisely deliver the individualized chemotherapeutic drugs for LGGs (Shein et al, 2016;Renault-Mahieux et al, 2021;Wang et al, 2021). Most of the hub genes correlated with cluster D had the function of immunocyte activation.…”