Optimization and in-vitro/in-vivo evaluation of doxorubicin-loaded chitosan-alginate nanoparticles using a melanoma mouse model
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The present study evaluates the potential of encapsulated doxorubicin to reduce both the viability of melanoma cells and the tumor growth in a mouse melanoma model. The prepared doxorubicin loaded chitosan/alginate nanoparticles possessed mean diameter around 300 nm and negative zeta-potential. Classical molecular dynamic simulations revealed that the high encapsulation efficiency (above 90%) was mainly due to electrostatic interaction between doxorubicin and sodium alginate, although dipole-dipole and hydrophobic interactions might also contribute. The in vitro dissolution tests showed slower doxorubicin release in slightly alkaline medium (pH = 7.4) and faster release in acid one (pH = 5.5), indicating that higher concentration of doxorubicin might reach the acidic tumor tissue. The free and the encapsulated doxorubicin decreased the viability of melanoma cell lines (B16-F10 and B16-OVA) in a similar degree. However, the cytotoxic effect of the encapsulated doxorubicin still occurred in the more resistant B16-F10 cells even after removing the extracellular drug. The experiments on a syngeneic melanoma mouse model revealed that free and encapsulated doxorubicin elicited the control of the tumor growth (dose of 3 mg/kg). Thus, the encapsulation of doxorubicin into chitosan/alginate nanoparticles could be considered advantageous because of the better intracellular accumulation and longer cytotoxic effect on the investigated melanoma cells.
Original language | English |
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Journal | International Journal of Pharmaceutics |
Volume | 556 |
Pages (from-to) | 1-8 |
Number of pages | 8 |
ISSN | 0378-5173 |
DOIs | |
Publication status | Published - 10 Feb 2019 |
Externally published | Yes |
Bibliographical note
Copyright © 2018 Elsevier B.V. All rights reserved.
- Alginates/chemistry, Animals, Antibiotics, Antineoplastic/administration & dosage, Cell Line, Tumor, Cell Survival/drug effects, Chemistry, Pharmaceutical/methods, Chitosan/chemistry, Doxorubicin/administration & dosage, Drug Carriers/chemistry, Drug Liberation, Female, Hydrogen-Ion Concentration, Hydrophobic and Hydrophilic Interactions, Melanoma, Experimental/drug therapy, Mice, Mice, Inbred C57BL, Molecular Dynamics Simulation, Nanoparticles, Particle Size
Research areas
ID: 255358590