Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines

Ms Farheen; Md Habban Akhter; Havagiray Chitme; Muath Suliman; Mariusz Jaremko; Abdul-Hamid Emwas

doi:10.1021/acsomega.3c01375

Surface-Modified Biobased Polymeric Nanoparticles for Dual Delivery of Doxorubicin and Gefitinib in Glioma Cell Lines

ACS Omega. 2023 Jul 26;8(31):28165-28184. doi: 10.1021/acsomega.3c01375. eCollection 2023 Aug 8.

Authors

Ms Farheen¹, Md Habban Akhter¹, Havagiray Chitme¹, Muath Suliman², Mariusz Jaremko³, Abdul-Hamid Emwas⁴

Affiliations

¹ School of Pharmaceutical and Population Health Informatics (SoPPHI), DIT University, Dehradun, Uttrakhand 248009, India.
² Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 62521, Saudi Arabia.
³ Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
⁴ Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

Abstract

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.