Synthesis of folate-chitosan nanoparticles loaded with ligustrazine to target folate receptor positive cancer cells

Abstract

In addition to its vasodilatory effect, ligustrazine (LZ) improves the sensitivity of multidrug resistant cancer cells to chemotherapeutic agents. To enhance the specificity of LZ delivery to tumor cells/tissues, folate-chitosan nanoparticles (FA-CS-NPs) were synthesized by combination of folate ester with the amine group on chitosan to serve as a delivery vehicle for LZ (FA-CS-LZ-NPs). The structure of folate-chitosan and characteristics of FA-CS-LZ-NPs, including its size, encapsulation efficiency, loading capacity and release rates were analyzed. MCF-7 (folate receptor-positive) and A549 (folate receptor-negative) cells cultured with or without folate were treated with FA-CS-LZ-NPs, CS-LZ-NPs or LZ to determine cancer-targeting specificity of FA-CS-LZ-NPs. Fluorescence intensity of intracellular LZ was observed by laser scanning confocal microscopy, and concentration of intracellular LZ was detected by HPLC. The average size of FA-CS-LZ-NPs was 182.7±0.56 nm, and the encapsulation efficiency and loading capacity was 59.6±0.23 and 15.3±0.16% respectively. The cumulative release rate was about 95% at pH 5.0, which was higher than that at pH 7.4. There was higher intracellular LZ accumulation in MCF-7 than that in A549 cells and intracellular LZ concentration was not high when MCF-7 cells were cultured with folate. These results indicated that the targeting specificity of FA-CS-LZ-NPs was mediated by folate receptor. Therefore, the FA-CS-LZ-NPs may be a potential folate receptor-positive tumor cell targeting drug delivery system that could possibly overcome multidrug resistance during cancer therapy.

Effect of Ligustrazine Nanoparticles on Th1/Th2 Balance by TLR4/MyD88/NF-κB Pathway in Rats with Postoperative Peritoneal Adhesion

“…Fortunately, with the development of biology and materials science, various anti-adhesion products such as biological scaffolds, membranes and drugs were applied on animals and in clinics for its prevention or decreasing of tissue adhesion [15] . Among of these strategies, nanoparticles with unique characteristic features were also widely used in adhesion formation [16] , peritoneal brosis [17] and cancer [18] .…”

Co-administration of macropinocytosis inhibitory nanoparticles (MiNP) for enhanced nanoparticle circulation time and target tissue accumulation following subcutaneous injection

“…We therefore investigated the transient effects of (+)MiNP by evaluating whether the inhibitor's effects would diminish within 100 h of the initial injection. have been used by other groups to successfully target these cells [31] . We therefore synthesized a [folate] -[PEG linker] -[palmitoleic acid lipid anchor] (FA-PEG-PA) amphiphilic construct for stable incorporation into self-assembled PEG-b-PPS micelles (Figure 1).…”

Nanostructured carriers as innovative tools for cancer diagnosis and therapy

“…More recently, poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles carrying paclitaxel and functionalized with folic acid were able to efficiently transport the drug in Caco-2 cells, paving the way to the delivery of drugs with poor oral bioavailability 83 . Another study demonstrated that folate-decorated chitosan nanoparticles were able to univocally deliver ligustrazine to cancer cells overexpressing folate receptors 84 . Concerning cancer imaging, many studies have shown that superparamagnetic iron oxide nanoparticles conjugated to folic acid can be exploited as contrast agents for magnetic resonance imaging (MRI) 85–87 .…”