New chitosan nanospheres for the delivery of 5-fluorouracil: preparation, characterization and in vitro studies.
The aim of this work was to develop new chitosan nanospheres for the delivery of 5-fluorouracil (5-FU). Drug loaded nanospheres were prepared using a technique derived from a combination of coacervation and emulsion droplet coalescence methods. The size and morphology of nanospheres were characterized by laser light scattering and transmission electron microscopy. The 5-FU interaction with chitosan nanospheres was investigated by DSC analysis and FT-IR spectroscopy. The in vitro release was studied by dialysis bag technique. Cytotoxicity of 5-FU loaded chitosan nanospheres was evaluated in vitro on HT29 and PC-3 cell lines. The effects of 5-FU loaded chitosan nanospheres on adhesion of tumor cells to human umbilical vein endothelial cells (HUVEC) were also investigated. 5-FU loaded chitosan nanospheres appeared with a spherical shape, with a mean diameter of about 200 nm and a negative zeta potential of about - 6.0 mV. The successful interaction between drug and chitosan nanosphere matrix was demonstrated by both DSC and FT-IR analyses. The quantitative determination of 5-FU was assayed by UV-Vis analysis. The encapsulation efficiency of 5-FU content was about 70%. A kinetic study of in vitro release demonstrated that the percentages of 5-FU delivered from nanospheres was approx. 10% after 3 hours. The in vitro studies showed that 5-FU loaded nanospheres were effective in reducing tumor cell proliferation in a time- and concentration-dependent manner. 5-FU nanospheres were also able to inhibit both HT29 and PC-3 adhesion to HUVEC after 48 hours of treatment.
Roberta
R
Cavalli
Federica
F
Leone
Rosalba
R
Minelli
Roberto
R
Fantozzi
Department of Drug Science and Technology, University of Torino, Via Pietro Giuria 9, 10125, Turin, Italy. roberta.cavalli@unito.it.
Chiara
C
Dianzani
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D048271:Chitosan / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D054118:Nanospheres / Q000008:administration & dosage*
D000964:Antimetabolites, Antineoplastic; D048271:Chitosan; D005472:Fluorouracil