Abstract
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.
Key words
Crocus sativus
- Iridaceae - saffron - crocin - PEGylated nanoliposome - antitumor activity - cancer
- C26 colon carcinoma
