Dual-Ligand Functionalized Core-Shell Chitosan-Based Nanocarrier for Hepatocellular Carcinoma-Targeted Drug Delivery
| Autor: | Marwan Emara, Ibrahim M. El-Sherbiny, Kholoud Arafa, Amr Hefnawy, Islam H Khalil |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
media_common.quotation_subject Biophysics Pharmaceutical Science Bioengineering 02 engineering and technology Pharmacology 010402 general chemistry 01 natural sciences Biomaterials Chitosan chemistry.chemical_compound In vivo Drug Discovery medicine Doxorubicin media_common Organic Chemistry General Medicine 021001 nanoscience & nanotechnology medicine.disease Lactobionic acid 0104 chemical sciences chemistry Targeted drug delivery Hepatocellular carcinoma Nanocarriers 0210 nano-technology medicine.drug |
| Zdroj: | International Journal of Nanomedicine. 15:821-837 |
| ISSN: | 1178-2013 |
| DOI: | 10.2147/ijn.s240359 |
| Popis: | Introduction Hepatocellular carcinoma represents a major health problem with the related death numbers still increasing. Active targeting is considered an attractive choice for the development of selective therapeutics with limited side effects and improved efficiency. In this study, we report the design, development and evaluation of a novel dual-ligand functionalized core-shell chitosan-based nanocarrier for the selective delivery of doxorubicin (DOX) for treatment of hepatocellular carcinoma (HCC). Methods Following factorial design experiments, DOX was initially complexed with negatively charged carboxymethyl chitosan-g-poly(acrylate) and then the complex was coated with a positively charged dual-ligand (lactobionic acid and glycyrrhetinic acid)-conjugated chitosan. The developed active targeting system was then tested in vitro on Hep-G2 cells using flow cytometry and fluorescence imaging. Results The obtained results proved the ability of the dual-ligand system to enhance the intracellular uptake of the drug by 4-fold and 8-fold after 4 hrs and 24 hrs of incubation, respectively. The efficiency of the dual-ligand functionalized nanoparticles was also tested in vivo on Wistar rats with induced liver tumors. Testing of serum biomarkers (albumin, creatinine, urea, alpha fetoprotein, ALT, AST and ALP) in addition to histopathological microscopic examination of liver, kidney and heart tissues confirmed the enhanced safety of the developed targeted nanocarrier system compared to the conventional DOX. Discussion The developed targeted system showed improved intracellular drug delivery and uptake as well as enhanced safety profile. The nanoparticles were formed based on electrostatic interactions providing the flexibility that allows their use as a model for delivery of other drugs and other targets. |
| Databáze: | OpenAIRE |
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