Akademik Veri Yönetim Sistemi
14th International Symposium on Pharmaceutical Sciences (ISOPS), Ankara, Türkiye, 25 - 28 Haziran 2024, ss.1-2
Introduction: Liposomes are spherical lipid vesicles, usually
50-500 nm in size, consisting of one or more lipid bilayers. Since they consist
of phospholipids, which are the building blocks of the body, they are
biocompatible and non-toxic vesicular drug carrier systems (1). Nanocochleates
are lipid-based, non-vesicular, stable, cylindrical, solid lipid bilayer-bearing
systems obtained by precipitating a negatively charged lipid and a cation
structure such as calcium. They are composed of phosphatidylserine, cholesterol
and calcium (2). It was aimed to produce liposome and nanocochleate containing
lenalidomide, an anticancer drug used in the treatment of cancers such as
multiple myeloma and non-hodgkin lymphoma (3), to carry out characterization
studies and to determine their cytotoxicity on the MDA breast cancer cell line.
Materials
and Methods: Lenalidomid was gifted from Deva. Liposome was
produced using 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) by the thin
layer hydration method. Nanocochleate was obtained by precipitating dioleoylphosphatidylserine
(DOPS), an anionic lipid, with the help of Ca+2 ions by adding CaCl2
(4). Formulations were characterized considering encapsulation efficiency, drug
release, particle size, polydispersity index, zeta potential, scanning electron
microscopy (SEM) images and cytotoxicity. In
vitro release studies performed by static method in distilled water for 48
hours. The cytotoxicity of different concentrations of lenalidomide (7.5-1000
µg/mL), and liposome and nanocochleat containing dose of lenalidomide with
anticancer effect (1000 µg/mL) were determined using the
3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the
MDA cell line at 24 and 48 hours.
Results: It
was observed from the SEM images that the liposomes were spherical and the
nanocochleates were cylindrical. Particle sizes of the liposome and
nanocochleat were 454.8±14.2 nm and 586.7±15.7 nm, and the zeta potentials were
-21.2±1.7 mV and -38.9±3.9 mV, respectively. They had favorable encapsulation
efficiency (77.3-83.4%). Drug release profiles were similar in both
formulations with high burst effect up to 6 hours (87.3% for the liposome,
84.8% for the nanocochleate) and prolonged release up to 48 hours. According to
MTT test results, lenalidomide-loaded liposomes caused higher cytotoxicity
(lower viability/34%) at 24 hours, while lenalidomide-loaded nanocochleate
allowed lower cytotoxicity (higher viability/41%). However, the nanocochleate
showed higher cytotoxicity (28.9% viability) than the liposome (30.8%
viability) at 48 hours.
Conclusions: In
conclusion, stable, nanosized lenalidomide-loaded liposome and nanocochleate
with desired and superior morphology, encapsulation efficiency, particle size,
zeta potential, in vitro release and
cytotoxicity properties have been successfully developed. While both the
formulations provided anticancer effects for up to 48 hours, it was concluded
that nanocochleate may be more suitable than liposome for long-term anticancer
effects.