The aim of the present study is to develop Doxorubicin–Erlotinib nanoparticles (Dox–Erlo NPs) and folate-armored Dox–Erlo-NP conjugates for targeting glioma cancer. Glioma is one of the most common progressive cancerous growths originating from brain glial cells. However, the blood–brain barrier (BBB) is only semi-permeable and is highly selective as to which compounds are let through; designing compounds that overcome this constraint is therefore a major challenge in the development of pharmaceutical agents. We demonstrate that the NP conjugates studied in this paper may ameliorate the BBB penetration and enrich the drug concentration in the target bypassing the BBB. NPs were prepared using a biopolymer with a double-emulsion solvent evaporation technique and functionalized with folic acid for site-specific targeting. Dox–Erlo NPs and Dox–Erlo-NP conjugates were extensively characterized in vitro for various parameters. Dox–Erlo NPs and Dox–Erlo-NP conjugates incurred a z-average of 95.35 ± 10.25 nm and 110.12 ± 9.2 nm, respectively. The zeta potentials of the Dox–Erlo NPs and Dox–Erlo-NP conjugates were observed at −18.1 mV and −25.1 mV, respectively. A TEM image has shown that the NPs were well-dispersed, uniform, de-aggregated, and consistent. A hemolytic assay confirmed hemocompatibility with the developed formulation and that it can be safely administered. Dox–Erlo-NP conjugates significantly reduced the number of viable cells to 24.66 ± 2.08% and 32.33 ± 2.51% in U87 and C6 cells, respectively, and IC50 values of 3.064 µM and 3.350 µM in U87 and C6 cells were reported after 24 h, respectively. A biodistribution study revealed that a significant concentration of Dox and Erlo were estimated in the brain relative to drug suspension. Dox–Erlo-NP conjugates were also stable for three months. The findings suggest that the developed Dox–Erlo-NP conjugates may be a promising agent for administration in glioma therapy.

Glioma is a malignant form of brain cancer that is challenging to treat due to the progressive growth of glial cells. To target overexpressed folate receptors in glioma brain tumors, we designed and investigated doxorubicin–gefitinib nanoparticles (Dox-Gefit NPs) and folate conjugated Dox-Gefit NPs (Dox-Gefit NPs-F). Dox-Gefit NPs and Dox-Gefit NPs-F were characterized by multiple techniques including Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1H NMR), and transmission electron microscopy (TEM). In vitro release profiles were measured at both physiological and tumor endosomal pH. The cytotoxicity of the Dox-Gefit NP formulations was measured against C6 and U87 glioma cell lines. A hemolysis assay was performed to investigate biocompatibility of the formulations, and distribution of the drugs in different organs was also estimated. The Dox-Gefit NPs and Dox-Gefit NPs-F were 109.45 ± 7.26 and 120.35 ± 3.65 nm in size and had surface charges of −18.0 ± 3.27 and −20.0 ± 8.23 mV, respectively. Dox-Gefit NPs and Dox-Gefit NPs-F significantly reduced the growth of U87 cells, with IC50 values of 9.9 and 3.2 μM. Similarly, growth of the C6 cell line was significantly reduced, with IC50 values of 8.43 and 3.31 μM after a 24 h incubation, in Dox-Gefit NPs and Dox-Gefit NPs-F, respectively. The percentage drug releases of Dox and Gefit from Dox-Gefit NPs at pH 7.4 were 60.87 ± 0.59 and 68.23 ± 0.1%, respectively. Similarly, at pH 5.4, Dox and Gefit releases from NPs were 70.87 ± 0.28 and 69.24 ± 0.12%, respectively. Biodistribution analysis revealed that more Dox and Gefit were present in the brain than in the other organs. The functionalized NPs inhibited the growth of glioma cells due to high drug concentrations in the brain. Folate conjugated NPs of Dox-Gefit could be a treatment option in glioma therapy.