17 Ther. Deliv. (2015) 6(1), 17–25 ISSN 2041-5990
Therapeutic
Delivery
Preliminary Communication
part of
10.4155/TDE.14.99 © 2015 Future Science Ltd
Aim: Our hypothesis was to prove that surface modifiers themselves can be used as
stabilizers and that their entrapment efficiency is directly influenced by the type of
stabilizers used. Materials & methods: Particle size and the polydispersity index of
the nanoparticles (NPs) were measured by dynamic light scattering, whereas the
morphology of the NPs was studied by scanning electron microscopy. Percentage
nanoparticle yield, entrapment efficiency and drug loading capacity were measured by
ultraviolet absorbance. The physical rigidity, robustness and drug releasing capability
of these NPs were also assessed. Conclusion: Physiochemical characterization and
the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay suggest that
polysorbate 80 has the dual capability of being a stabilizer and a surface modifier in
addition to having better drug entrapment properties than Pluronic
®
188. Disulfiram,
the drug that was loaded on these NPs, is also observed for the first time to show
significant anticancer potential against hepatocellular carcinoma (Hep3B) cell lines.
Keywords: anticancerpotential•disulfram•PLGAnanoparticles•Pluronic188
•polysorbate80•stabilizers•TritonX-100
Polymeric nanoparticles (NPs) generally have
three important components: a polymer, a
stabilizer and a surface-modifying agent.
The selection of the combination of stabiliz-
ers and polymers is critical for the synthesis
of poly(lactic-co-glycolic acid) (PLGA) NPs
that have maximum entrapment, stability and
drug delivering capabilities of the said com-
pound/drug. In addition, for the generation
of biologically compatible NPs, stabilizers
and surface modifications play an important
role. PLGA is a linear chain of alternating lac-
tic and glycolic acids that, upon entering the
biological systems, become disintegrated in a
phase manner mainly by hydrolytic enzymes
and – to an extent – by physiological envi-
ronmental factors, such as temperature and
pH [1] . Surface modification of NPs helps
with the evasion of the mononuclear phago-
cytic system (MPS), thus improving travel
time in the blood circulation [2] .
Disulfiram (DSF) is a well-known
antialcoholic drug [3] . The quest for the
development of cost-effective anticancer
drugs has led to the study of the antican-
cer potentials of old, established drugs that
have minimal side effects and are no longer
patented. DSF has been reported to have
significant anticancer effects through more
than one pathway in a number of preclini-
cal trials [4] . However, similarly to any drug,
DSF may also have a generalized effect on
the whole organism, rather than being more
localized, which results in inefficient delivery
and high interference from normal cells.
Stabilizers have amphiphilic properties.
The quality of the stabilizer may be modified
based on the ratio of hydrophobic to hydro-
philic entities in its composition. Pluronics
are a family of nonionic surfactants that are
made of polyoxypropylene (the hydrophobic
entity) and polyoxyethylene (the hydrophilic
entity). Pluronic
®
188 (Sigma Aldrich, Ban-
galore, India) is composed of 80% polyoxy-
ethylene, which is responsible for its hydro-
philic properties that are necessary for it to
Influence of stabilizers on the production
of disulfiram-loaded poly(lactic-co-glycolic
acid) nanoparticles and their anticancer
potential
Muddasarul Hoda
1
, Shamim
Akhtar Sufi
1
, Garima Shakya
1
,
Kumarvel Mohan Kumar
1
& Rukkumani Rajagopalan*
,1,2
1
DepartmentofBiochemistry
&MolecularBiology,SchoolofLife
Sciences,PondicherryUniversity,
Puducherry605014,India
2
DepartmentofBiotechnology,University
ofMadras,GuindyCampus,Chennai,
Tamilnadu600025,India
*Authorforcorrespondence:
Tel.:+919677847337
Fax:+914132655255
ruks2k2@yahoo.co.in