Harnessing Folate-Functionalized Nasal Delivery of Dox–Erlo-Loaded Biopolymeric Nanoparticles in Cancer Treatment: Development, Optimization, Characterization, and Biodistribution Analysis

Abstract

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.

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

“…Moreover, the authors observed a noticeable variation in the biodistribution of Dox in the brain from Dox-Gefit NPs-F compared to the Dox-Erlo NP conjugates. It was noted a significant improvement in the biodistribution of Dox in the brain, i.e., 0.562 μg/mg of the brain tissue from Dox-Gefit NPs-F compared to 40 ng/g of the brain tissue from Dox-Erlo NPs conjugates, indicating the superior therapeutic efficacy of the Dox-Gefit NPs-F over Dox-Erlo NP conjugates ( p < 0.01) …”

“…The MTT assay outcomes suggested that Dox-Gefit NPs-F successfully decreased cell viability with increasing concentration of the drug in the NPs owing to improved drug delivery into the cells. , Further, the combination index value was investigated, which indicated the synergistic effect of both drugs from Dox-Gefit NPs-F, and it was verified using the Chou–Talalay method. , It has been reported that tumor cells overexpressing the folate receptor could be an easy route of access for cytotoxic drugs. , In the current study, folate ligation to Dox-Gefit NPs resulted in a higher brain concentration compared to bare NPs, validating the higher efficacy of Dox-Gefit NPs-F. There was also remarkable cytotoxicity of Dox-Gefit NPs-F compared to bare NPs, comparable to a previous study executed by Jingjing et al and Mondal and associates. , …”

Design-of-Experiment-Assisted Fabrication of Biodegradable Polymeric Nanoparticles: In Vitro Characterization, Biological Activity, and In Vivo Assessment

“…As per the ASTMF756-00 (2000) standard, the materials considered to be nonhemolytic, when the percentage hemolysis is less than 2%. This could be attributed to the natural sources of the biomaterial used in the study …”

Tadpole-Like Anisotropic Polymer/Lipid Janus Nanoparticles for Nose-to-Brain Drug Delivery: Importance of Geometry, Elasticity on Mucus-Penetration Ability

“…The samples were subsequently centrifuged for 10 min at 2000 rpm. The supernatant was analyzed to determine the release of hemoglobin from hRBC at 540 nm using UV–visible spectroscopy. − The hemolysis % values were determined using eq h e m o l y s i s .25em % = A normalsample − A normalnegative_control A normalpositive_control − A normalnegative_control where A sample , A negative_control , and A positive_control are the absorbances of the sample, negative control, and positive control, respectively.…”