Cisplatin and paclitaxel co-delivered by folate-decorated lipid carriers for the treatment of head and neck cancer

Abstract

Context: For head and neck cancer therapy, co-delivery of two drugs, cisplatin (DDP) plus paclitaxel (PTX), are more effective than single drug therapy. Lipid carriers are promising drug carriers for anti-cancer delivery.

Objective: The aim of this study is to construct a folate (FA) decorated nanostructured lipid carriers (NLCs) as nanocarriers for DDP and PTX delivery.

Materials and methods: In this study, DDP and PTX were incorporated into NLCs. Folate-PEG-DSPE (FA-PEG-DSPE) was synthesized and decorated the drugs-loaded NLCs (FA-DDP/PTX NLCs). Their average size, zeta potential, drug encapsulation efficiency, drug loading capacity, and in vitro drug release were evaluated. Head and neck cancer cells (FaDu cells) were used for the testing of in vitro cytotoxicity, and in vivo transfection efficiency of NLC was evaluated on mice bearing FaDu cells model.

Results: The size of FA-DDP/PTX NLCs was around 127 nm, with a positive zeta potential of 26.7 mV. FA-DDP/PTX NLCs showed the highest cytotoxicity and synergistic effect of two drugs in head and neck cancer cells (FaDu cells) in vitro. The in vivo study revealed the greatest anti-tumor activity than all the other formulations in murine-bearing head and neck cancer model.

Discussion and conclusion: FA-DDP/PTX NLCs effectively improves anticancer efficiency for head and neck cancer in vitro and in vivo. The constructed NLCs could be used as a novel carrier to co-delivery DDP and PTX for head and neck cancer therapy.

Keywords: Cisplatin; co-delivery; head and neck cancer; lipid carriers; paclitaxel.

Figure 1.

(1) Scheme graph of the construction of FA-DDP/PTX NLCs; (2) TEM image of FA-DDP/PTX NLCs.

Figure 2.

(1) Changes in size in the presence of serum: (1) FA-DDP/PTX NLCs, (2) DDP/PTX NLCs, (3) PTX NLCs, (4) DDP NLCs; (2-2) changes in DEE in the presence of serum: (1) DDP DEE of FA-DDP/PTX NLCs, (2) PTX DEE of FA-DDP/PTX NLCs, (3) DDP DEE of DDP/PTX NLCs, (4) PTX DEE of DDP/PTX NLCs, (5) PTX DEE of PTX NLCs, and (6) DDP DEE of DDP NLCs.

Figure 3.

(1) In vitro DDP and PTX release at pH 7.4; (2) in vitro DDP and PTX release at pH 5.0: (1) DDP releases from FA-DDP/PTX NLCs, (2) DDP release from DDP/PTX NLCs, (3) PTX release from FA-DDP/PTX NLCs, and (4) PTX release from DDP/PTX NLCs.

Figure 4.

In vitro cell viabilities: (1) FA-DDP/PTX NLCs, (2) DDP/PTX NLCs, (3) PTX NLCs, (4) DDP NLCs, (5) PTX solutions, and (6) DDP solutions.

Figure 5.

(1) In vivo DDP tissue distribution of FA-DDP/PTX NLCs; (2) in vivo PTX tissue distribution of FA-DDP/PTX NLCs.

Figure 6.

(1) The tumor growth curves; (2) body weight change curves: (1) FA-DDP/PTX NLCs, (2) DDP/PTX NLCs, (3) PTX NLCs, (4) DDP NLCs, (5) PTX solutions, (6) DDP solutions, and (7) 0.9% saline.