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Glioblastoma (GBM) is the most aggressive primary malignant tumor of the central nervous system. Although temozolomide (TMZ) is the first-line treatment, its therapeutic efficacy is limited by tumour resistance, poor selectivity, and systemic adverse side effects. In this context, biomimetic nanoparticles coated with cell membranes have emerged as a promising strategy to improve targeted drug delivery. This study aimed develop and characterize poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with TMZ and coated with glioblastoma-derived cell membranes to evaluate their physicochemical properties, stability, encapsulation efficiency, and in vitro biological activity. Nanoparticles were prepared using the double emulsion (W/O/W) technique and coated with isolated U87 glioblastoma cell membranes by membrane extrusion. Characterization included dynamic light scattering (DLS), zeta potential, nanoparticle tracking analysis (NTA), atomic force microscopy (AFM), and Fourier-transform infrared spectroscopy (FTIR). Stability was monitored for 43 days at 4°C. Encapsulation efficiency was determined by high-performance liquid chromatography (HPLC), while biological activity was assessed using the MTT and trypan blue exclusion assays in tumour and non-tumour cell lines. The nanoparticles exhibited mean diameters ranging from 233 to 251 nm, low polydispersity (PDI ≤ 0.136), and good physicochemical stability throughout storage. Membrane coating reduced the zeta potential to approximately −8 mV, confirming successful surface modification. FTIR analysis revealed a decrease in the intensity of the carbonyl band (~1750 cm⁻¹), consistent with cell membrane coating, whereas AFM confirmed a predominantly spherical morphology. TMZ encapsulation efficiency ranged from 35.5% to 44.8%. The developed biomimetic nanoparticles exhibited suitable physicochemical characteristics and demonstrated potential as a targeted delivery platform for temozolomide in glioblastoma treatment. This strategy represents a promising approach to enhance therapeutic efficacy while reducing the systemic adverse effects associated with conventional chemotherapy.
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