Co-delivery of docetaxel and palmitoyl ascorbate by liposome for enhanced synergistic antitumor efficacy

Abstract

Palmitoyl ascorbate (PA) as an antioxidant has the potential for the treatment of cancer. In the present study, a nanocarrier system was developed for co-delivery of docetaxel (DOC) with palmitoyl ascorbate and the therapeutic efficacy of a combination drug regimen was investigated. For this purpose, different ratios of docetaxel and palmitoyl ascorbate were co-encapsulated in a liposome and they all showed high encapsulation efficiency. The average diameters of the liposomes ranged from 140 to 170 nm. Negative zeta potential values were observed for all systems, ranged from −40 mV to −56 mV. Studies on drug release and cellular uptake of the co-delivery system demonstrated that both drugs were effectively taken up by the cells and released slowly. Moreover, the liposome loading drugs with DOC/PA concentration ratio of 1:200 showed the highest anti-tumor activity to three different types of tumor cells. The higher in vivo therapeutic efficacy with lower systemic toxicity of the DOC-PA200-LPs was also verified by the H22 tumor bearing mice model. Our results showed that such co-loaded delivery systems could serve as a promising therapeutic approach to improve clinical outcomes against hepatic carcinoma.

Docetaxel-trastuzumab stealth immunoliposome: development and in vitro proof of concept studies in breast cancer

“…Therefore, although the first or second generation of liposomes displayed improved pharmacokinetics (ie, decreased clearance and higher tumor accumulation), [12][13][14] further development of nanoparticles is still an ongoing story with taxanes. Thus, more sophisticated forms have been developed such as co-loaded liposomes (eg, docetaxel + palmitoyl ascorbate, 15 paclitaxel + rapamycin, 16 docetaxel + BCL-2 SiRNA 17 ), triggered liposomes (eg, pH sensitive 18 or thermosensitive 19 ) and targeted liposomes. Many moieties (eg, small-molecule ligands, peptides 20 and monoclonal antibodies) have been used over the last years to actively target cancer cells through different strategies, including targeting several receptors like folate receptors, 21,22 integrin 23 and transferrin.…”

Photosynthesis-inspired H2 generation using a chlorophyll-loaded liposomal nanoplatform to detect and scavenge excess ROS

“…Lip NPs were prepared by the thin-film hydration technique 40 . Briefly, DPPC, cholesterol, and DSPE-PEG2000 in a molar ratio of 6:4:0.5 were mixed with Chla (60 μM) in chloroform; then, lipid film was obtained by using the rotavap to remove the organic solvent.…”

<p>Liver-targeted liposomes for codelivery of curcumin and combretastatin A4 phosphate: preparation, characterization, and antitumor effects</p>

“…After 2 weeks, the mice had developed ascites tumors. Second, cells from the H22 liver cancer ascites-tumor sources were collected in sterile conditions and diluted to 4×10 6 tumor cells/mL with normal saline. Approximately 0.2 mL of the suspension was subcutaneously inoculated into the flanks of mice.…”

“…2,3 The effectiveness of combination therapy is supported by clinical research, which shows superior antitumor efficacy than single-drug therapy via different antitumor approaches. [4][5][6] Antiangiogenesis, a promising antitumor strategy blocking the development of tumor blood vessels, is widely accepted. 7 Therefore, the combination of chemotherapeutics with antiangiogenic drugs is expected to improve therapeutic efficacy for HCC.…”