APPROACHES TO PHARMACEUTICAL ANALYSIS
OF AN INNOVATIVE LIPOSOMAL PREPARATION
FOR TREATING HEPATITIS C
V. V. Smirnov,
L. M. Krasnykh,
I. P. Shilovskii,
A. P. Ryzhenkova,
M. R. Khaitov,
and V. N. Drozdov
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 52, No. 3, pp. 59 – 61, March, 2018.
Original article submitted January 31, 2018.
The composite Y14/siUTR, a complex consisting of cationic lipopeptide Y14 as an excipient and pharmaceu
tical substance of small interfering RNA targeted against the UTR region of hepatitis C virus (siUTR), was in
vestigated. The composite was intended to inhibit the hepatitis C virus replication cycle. The present work was
aimed at developing pharmaceutical analytical methods for the components of this composite using
HPLC-UV and UV spectroscopy.
Keywords: hepatitis C, liposomes, RNA interference, HPLC-UV, spectrophotometry.
siRNA and a cationic lipopeptide designed in a prelimi-
nary stage allowed the feasibility of creating medicines that
suppress hepatitis virus C (HVC) replication via RNA inter-
ference to be evaluated [1, 2].
Hepatitis viruses present serious medical and social
problems for world healthcare because of their ubiquitous
distribution and high incidence. According to the WHO, one
third of the global population is infected with various types
of hepatitis viruses. Experts estimate 400 million people
carry hepatitis virus B (HVB); 300 million, HVC. In Russia,
the respective numbers are 5 and 2 million, of which up to
97.8% are 19 – 39 years of age .
A distinguishing feature of HVC is its ability to persist in
vivo for long periods, which is responsible for high levels of
chronic infection. Chronic hepatitis C (CHC) accounts for
>70% of all chronic liver diseases. Thus, the infection index
for CHC in 2014 in the RF was 38.38 per 100,000 people and
was 3.5 times greater than that for chronic hepatitis B. In
Russia as a whole, the number of CHC cases increased by
19% as compared with 2005. HVC is the etiological factor in
40% of liver cirrhosis cases and 60 – 70% of hepatocellular
Enormous progress in understanding the virus life cycle
and developing new antiviral preparations has been achieved
in the 25 years since the discovery of HVC, despite the lack
of adequate research models. A sustained virologic response
(SVR) was obtained in only 6% of the cases since the start of
interferon monotherapy in the 1980s. The era of direct acting
antiviral preparations that provide an SVR in >70% of the
cases is just beginning . Now, we are on the threshold of a
new era in HVC therapy where combinations of direct acting
antiviral preparations without interferon will be used in al
most 100% of the cases .
Preparations targeted at host-cell elements involved in
virus replication in addition to direct acting antiviral prepara
tions are under development. They possess broad spectra of
action against various virus genotypes and present a high
barrier to the development of resistance because they are tar
geted at host-cell elements and not viral factors. Two prepa
rations of this type are currently in clinical trials, i.e., a spe
cific inhibitor of cyclophilin A (Alisporivir) and a
microRNA-122 antagonist (miravirsen). The active ingredi
ent of the latter consists of synthetic small interfering RNA
(siRNA) targeted at cellular microRNA miR-122 .
RNA interference is a natural mechanism for regulating
gene expression in cells by Dicer enzyme and siRNA. RNA
Pharmaceutical Chemistry Journal, Vol. 52, No. 3, June, 2018 (Russian Original Vol. 52, No. 3, March, 2018)
0091-150X/18/5203-0254 © 2018 Springer Science+Business Media, LLC
Scientific Center for Expert Evaluation of Medicinal Products, Ministry of
Public Health of the Russian Federation, 8/2 Petrovskii Blvd., Moscow,
Institute of Immunology, Federal Medico-Biological Agency of the Rus
sian Federation, Moscow, 115478 Russia.
I. M. Sechenov First Moscow State Medical University, Ministry of
Health of Russia (Sechenov University), Moscow, 119991 Russia.