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[Display omitted] This study aims to overcome physiological barriers and increase the therapeutic index for the treatment of glioblastoma (GBM) tumors by using Paclitaxel (PTX) loaded Poly(lactic co-glycolic acid) nanoparticles (PTX-PLGA-NPs) and Doxorubicin (DOX) loaded Poly (lactic co-glycolic acid) nanoparticles (DOX-PLGA-NPs). The hydrodynamic diameter of nanoparticles (NPs) was characterized by dynamic light scattering (DLS) which was 94 ± 4 nm and 133 ± 6 nm for DOX-PLGA-NPs, and PTX-PLGA-NPs, respectively. The zeta potential for DOX-PLGA-NPs and PTX-PLGA-NPs were −15.2 ± 0.18 mV and −17.3 ± 0.34 mV, respectively. The cytotoxicity of PTX-PLGA-NPs and DOX-PLGA-NPs was augmented compared to DOX and PTX on C 6 GBM cells. The Lactate dehydrogenase (LDH) tests for various formulations were carried out. The results indicated that the amount of released LDH was 262 ± 7.84 U.L-1 at the concentration of 2 mg/mL in the combination therapy, which was much higher than other groups (DOX-PLGA-NPs (210 ± 6.92 U.L-1), PTX-PLGA-NPs (201 ± 8.65 U.L-1), DOX (110 ± 9.81 U.L-1), PTX (95 ± 5.02 U.L-1) and PTX + DOX (67 ± 4.89 U.L-1)). MRI results of the combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs indicated that GBM tumor size decreased considerably compared to the other formulations. Also, combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs demonstrated a longer median survival of more than 80 days compared to PTX (38 days), DOX (37 days) and PTX + DOX (48 days), PTX-NPs (58 days) and DOX-NPs (62 days). The results of locomotion, body weight, rearing and grooming assays indicated that combination therapy of PTX-PLGA-NPs and DOX-PLGA-NPs had the most positive effect on the movements of rats compared to the other formulations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] The aim of this work is to co-load paclitaxel (PTX) and etoposide (ETP) in methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (mPEG-PLGA NPs) to overcome pharmacokinetics and physiological limitations and enhance therapeutic efficacy for treating intracranial glioblastoma. Both drugs were loaded into mPEG-PLGA NPs by a nano-precipitation method. The resultant NPs demonstrated an enhanced cytotoxic effect indicated by lower IC 50 values and augmented cell apoptosis to U87 and C6 glioma cell lines compared to both free drugs. Additionally, blood compatibility assays showed that the PTX/ETP co-loaded mPEG-PLGA NPs did not induce blood hemolysis, blood clotting, or platelet aggregation. In vivo anti-glioma efficacy evaluation in rats bearing intracranial C6 glioma revealed a superior anti-glioma activity for the treatment with PTX/ETP co-loaded mPEG-PLGA NPs compared to other formulations, particularly a significantly longer median survival, 76 days compared to 36 days for free PTX and 37 days for free ETP treatment, respectively, and higher tumor regression, proved by magnetic resonance imaging (MRI). [ABSTRACT FROM AUTHOR]