Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889
part of
Research Article
10.2217/nnm-2016-0321 © 2017 Future Medicine Ltd
Aim: To improve the bioavailability and anticancer potential of suberoylanilide
hydroxamic acid (SAHA) by developing a drug-loaded polymeric nanomicellar system.
Methods: SAHA-loaded Poly(ethylene glycol)-block-poly(caprolactone) (PEG-PCL)
micelles were developed, and physico-chemically characterized. In vitro cellular
uptake, viability and apoptosis-inducing ability of the SAHA-PEG-PCL micelles were
investigated. In vivo anticancer activity was evaluated in C57BL/6 mice-bearing tumor.
Results: The SAHA-PEG-PCL micelles had optimum size ( ∼130 nm) with an entrapment
efficiency of approximately 67%. The SAHA-PEG-PCL induced stronger cell cycle arrest
in G2/M phase leading to higher rate of apoptosis compared to free SAHA. SAHA-
PEG-PCL demonstrated significant tumor suppression compared to free SAHA in vivo.
Conclusion: The physicochemical properties and the antitumor efficacy of SAHA were
improved by encapsulating in polymeric micelles.
First draft submitted: 31 August 2016; Accepted for publication: 18 October 2016;
Published online: 23 November 2016
Keywords: anticancer•drugdelivery•in vivoeffcacy•polymericmicelles•SAHA
Cancer is one among the major causes of
death worldwide. Despite the advances in
treatment options for cancer patients, the
incidence of cancer globally is suspected to
increase in coming years [1–3] . The epigenetic
control of gene expression has been shown
to play an important role in cancer. There-
fore, modifying the epigenetic environment
of tumors is an important addition to the
pool of anticancer strategies. Among various
epigenetic modulators, a group of enzymes,
histone deacetylases (HDACs) is known to
alter the epigenetic factors involved in the ini-
tiation, progression and resistance of cancer
cells. There are 18 known HDACs in humans
grouped into four classes based on their simi-
larity to yeast HDACs. HDAC inhibitors are
relatively new class of anticancer agents which
act by hyper-acetylation of histone and non-
histone proteins, which act as substrates to
HDAC and are responsible for cell differen-
tiation and growth [4–6] . The mechanism of
action of HDAC inhibitors include induction
of cell death, cell cycle arrest, senescence, dif-
ferentiation and autophagy caused by altering
the gene expression and/or post-translational
modification of proteins [7–10] .
Over the past decade, HDACs have
become promising therapeutic targets for
cancer. Changes in the levels of acetylation
and over-expression of various HDACs have
been reported in different cancer cell lines
and tumor tissues [8] . HDAC inhibitors were
reported to be selective toward cancerous
cells over normal cells due to overexpression
of HDACs in cancer cells. Recently, they are
being evaluated clinically in various solid
and hematologic malignancies [10,11] . HDAC
inhibitors are also being tested for synergistic
or additive effect along with other chemo-
therapeutic agents in various cancers [12–15] .
SAHA (suberoylanilide hydroxamic acid;
Vorinostat; Zolinza
®
), is the first HDAC
inhibitor approved by the US FDA for treat-
Polymeric micelles of suberoylanilide
hydroxamic acid to enhance the anticancer
potential in vitro and in vivo
Sri Vishnu Kiran
Rompicharla
1,‡
, Prakruti
Trivedi
1,‡
, Preeti Kumari
1
,
Pratyusha Ghanta
1
, Balaram
Ghosh
1
& Swati Biswas*
,1
1
DepartmentofPharmacy,Birla
InstituteofTechnology&Science-Pilani,
HyderabadCampus,Shameerpet,
Hyderabad,Telangana500078,India
*Authorforcorrespondence:
Tel.:+914066303630
swati.biswas@hyderabad.bits-pilani.ac.in
‡
Theseauthorscontributedequallyand
shouldbeconsideredfrstauthors
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