New Chitosan Nanospheres for the Delivery of 5-Fluorouracil: Preparation, Characterization and in vitro Studies

Abstract

The aim of this work is 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.

‘In Vitro’, ‘In Vivo’ and ‘In Silico’ Investigation of the Anticancer Effectiveness of Oxygen-Loaded Chitosan-Shelled Nanodroplets as Potential Drug Vector

“…Moreover, the cytotoxicity of chitosan and its derivatives toward tumor cells has been reported by several authors (22)(23)(24)(25)(26)(27)(28). Interestingly, cationic chitosan nanoparticles have been already exploited as effective nanocarriers due to their ability to be easily internalized by different cell types (29)(30)(31). Previously, our group prepared 5-fluorouracil-loaded chitosan nanoparticles, able to increase the cytotoxicity of the drug in vitro (32) The critical role of ROS in nanoparticle-mediated cytotoxicity and genotoxicity has been reported by several researchers (38)(39)(40)(41)(42).…”

Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

“…Recently, Cavalli et al (2014) formulated chitosan nanospheres with 5-fluorouracil using a combination of coacervation and emulsion droplet coalescence methods [69]. The resulting 5-FU-loaded chitosan nanospheres were not only able to reduce the proliferation of HT29 (Human colorectal adenocarcinoma) and PC-3 (Human prostate cancer-3) tumor cell lines in a time- and concentration-dependent manner but also inhibited their adhesion to human umbilical vein endothelial cells (HUVEC).…”

Acyclovir-Loaded Chitosan Nanospheres from Nano-Emulsion Templating for the Topical Treatment of Herpesviruses Infections

“…To obtain the nanospheres, the nano-emulsion was dropped by a syringe using a roller pump in a sodium citrate aqueous solution (0.1 M) under stirring. This semi-automatic technique ensures more reproducibility for the preparation process, which was previously reported [ 19 ]. After completing the drift phase, the system was centrifuged and washed three times with water.…”

“…Chitosan has been exploited for the delivery of acyclovir by Hasanovic et al who developed chitosan-tripolyphosphate nanoparticles to enhance the chemical stability of the drug [ 24 ]. Chitosan nanospheres with enhanced characteristic were prepared by combining a previous tuned method based on ionic gelation [ 19 ] and the nano-emulsion templating method [ 26 ]. This peculiar experimental set-up permitted to obtain stable chitosan nanospheres is able to load acyclovir to a great extent.…”