Paclitaxel/methotrexate co-loaded PLGA nanoparticles in glioblastoma treatment: Formulation development and in vitro antitumor activity evaluation

AimThe aim of this study was to improve the therapeutic index of chemotherapeutic drugs on glioblastoma cells through an improved co-drug delivery system. Materials and methodsMethotrexate (MTX) and paclitaxel (PTX) were co-loaded into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with polyvinyl alcohol (PVA) and Poloxamer188 (P188). Key findingsThe mean size of the NPs was about 212 nm, with a zeta potential of about −15.7 mV. Encapsulation efficiency (EE%) and drug loading (DL%) were determined to be 72% and 4% for MTX and 85% and 4.9% for PTX, respectively. The prepared NPs were characterized by differential thermal analysis (DTA) and thermogravimetric analysis (TGA). Moreover, an in vitro sustained release profile was observed for both drug loaded PLGA NPs. Glioblastoma cellular uptake of the NPs was confirmed by fluorescence microscopy and cell survival rate was investigated through the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method after 48 h of incubation showing IC50 values of 24.5 μg·mL−1 for PTX and 9.5 μg·mL−1 for MTX for the MTX/PTX co-loaded PLGA nanoparticles coated with PVA/P188 (Co-2 NPs). Apoptosis and necrosis were also studied via flow cytometry, the lactate dehydrogenase (LDH) assay and the amount of anti-apoptotic protein (Bcl-2) expression. Blood compatibility of the co-delivery of PTX and MTX loaded PLGA NPs was investigated using a hemolysis method as well. SignificanceThe co-delivery of PTX and MTX loaded PLGA NPs is promising for the treatment of glioblastoma compared to their respective free drug formulations and, thus, should be further investigated.This work was supported by Tehran University of Medical Sciences, Grant No. 96-01-87-34138, Iran

PLGA Nanoparticles Loaded with Cinnamon Extract and Coated with PVA/Poloxamer188

Cinnamon extract has received significant attention due to its significant antibacterial, antifungal, antioxidant, and even anti-cancer properties. The purpose of this study was to create cinnamon-extract-loaded PLGA nanoparticles and evaluate their physiochemical characteristics and cytotoxicity against the C6 cell line. Physiochemical characteristics, such as the mean diameter, zeta potential, and drug loading potential, were measured. The antioxidant activity and cytotoxicity of nanoparticles were investigated by DPPH and MTT studies, respectively. The mean diameter of nanoparticles was 120 ± 24 nm. The antioxidant activity of the cinnamon extract was mostly preserved in nanoparticles and the toxicity effect on cancer cells was investigated

Investigation of Effective Parameters on Size of Paclitaxel Loaded PLGA Nanoparticles

Purpose: The size of polymeric nanoparticles is considered as an effective factor in cancer therapy due to enterance into tumor tissue via the EPR effect. The purpose of this work was to investigate the effective parameters on poly(lactic-co-glycolic acid)-paclitaxel (PLGA –PTX) nanoparticles size. Methods: We prepared PLGA-PTX nanoparticles via single emulsion and precipitation methods with variable paremeters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration. Results: PLGA-PTX nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The results exhibited that the diameter of nanoparticles enhanced with increasing drug, polymer and PVA concentrations whereas organic to aqueous phase volume ratio and sonication time required to the optimization for a given size. Conclusion: The precipitation method provides smaller nanoparticles compared to emulsion one. Variable parameters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration affect diameter of nanoparticles