Crocin is a pharmacologically active component of Crocus sativus. It is an unusual water-soluble
carotenoid responsible for the red color of saffron. In various studies, the anticancer effect of saffron and its constituents has been established.
Polyethylene glycolated nanoliposomes with a size range up to 200 nm are suitable for encapsulation of cytotoxic drugs and can target
tumors passively through the enhanced permeation and retention effect. The aim of this study was to develop a nanoliposomal formulation containing
crocin with a higher therapeutic index for the treatment of
cancer. Four formulations of
polyethylene glycolated nanoliposomes containing 25 mg/ml
crocin were prepared with hydrogenated soy
phosphatidylcholine,
cholesterol, and methoxy-
polyethylene glycol (MW 2000)-distearoylphosphatidylcholine at different molar ratios by a
solvent evaporation method plus extrusion. Then the
liposomes were characterized for their size, zeta potential,
crocin encapsulation, release properties, and in vitro cytotoxicity against C26 colon
carcinoma cells. Based on in vitro results, the best formulation was selected for an in vivo study, and its antitumor activity was evaluated in BALB/c mice bearing C26 colon
carcinoma. The IC50 of
crocin itself against C26 colon
carcinoma was 0.73 mM. The characterization of the best formulation was as follow: Z-average size: 127.6 ± 1.5 nm; polydispersity index: 0.087 ± 0.018; zeta potential: - 21.7 mV ± 6.7; % encapsulation: 84.62 ± 0.59; % release after 168 hours in RPMI 1640 containing 30 % FBS: 16.26 ± 0.01 %. Liposomal
crocin at doses of 50 and 100 mg/kg significantly decreased
tumor size and increased survival rate compared with PBS and
crocin in
buffer (100 mg/kg) groups. The results of this study indicated that liposomal encapsulation of
crocin could increase its antitumorigenic activity. Thus, to obtain an optimal dose for use in humans, the formulation merits further investigation.