TY - JOUR

T1 - Optimization and in-vitro/in-vivo evaluation of doxorubicin-loaded chitosan-alginate nanoparticles using a melanoma mouse model

AU - Yoncheva, Krassimira

AU - Merino, Maria

AU - Shenol , Aslihan

AU - Daskalov, Nikolay T

AU - Petkov, Petko St

AU - Vayssilov, Georgi N

AU - Garrido, Maria J

N1 - Copyright © 2018 Elsevier B.V. All rights reserved.

PY - 2019/2/10

Y1 - 2019/2/10

N2 - 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.

AB - 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.

KW - Alginates/chemistry

KW - Animals

KW - Antibiotics, Antineoplastic/administration & dosage

KW - Cell Line, Tumor

KW - Cell Survival/drug effects

KW - Chemistry, Pharmaceutical/methods

KW - Chitosan/chemistry

KW - Doxorubicin/administration & dosage

KW - Drug Carriers/chemistry

KW - Drug Liberation

KW - Female

KW - Hydrogen-Ion Concentration

KW - Hydrophobic and Hydrophilic Interactions

KW - Melanoma, Experimental/drug therapy

KW - Mice

KW - Mice, Inbred C57BL

KW - Molecular Dynamics Simulation

KW - Nanoparticles

KW - Particle Size

U2 - 10.1016/j.ijpharm.2018.11.070

DO - 10.1016/j.ijpharm.2018.11.070

M3 - Journal article

C2 - 30529664

VL - 556

SP - 1

EP - 8

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

ER -