Materials Sciences and Applications, 2010, 1, 36-38
doi:10.4236/msa.2010.11007 Published Online April 2010 (http://www.SciRP.org/journal/msa)
Preparation of Star-Shaped Polylactic Acid Drug
Carrier Nanoparticles
Michele Marini
Mazal-TOV S. A. S., Via Carmelitane Scalze – Modena, Italy.
Received February 13th, 2010; revised March 13th, 2010; accepted March 15th, 2010.
ABSTRACT
Drug carrier biocompatible and biodegradable nanoparticles of about 15 nm were prepared by solvent evaporation
technique from star-shaped poly(D,L-lactide) synthesized using dipentaerythritol as core and Tin (II) ethylhexanoate as
catalyst.
Keywords: PLA, Nanoparticles, Drug-Carriers
1. Introduction
It is well known that the penetration of substances into
the brain is limited by the blood-brain barrier (BBB) wh-
ich is formed by the endothelium of the brain vessels, the
basal membrane and neuroglial cells [1]. Because of this
most drugs do not pass the BBB. It is widely accepted
that only compounds which are unionized at physiologi-
cal pH, are lipophilic, and of low molecular mass can
cross the BBB by diffusion mechanisms, and other com-
pounds, such as amino acids, neuropeptides, and hexoses,
need specific carrier proteins to pass into the brain [1].
To overcome the limited access of drugs to the brain,
several methods have been employed to achieve BBB
penetration. The use of drug carriers such as liposomes
[2] and nanoparticles for targeted drug delivery has been
examined.
Biodegradable polymers have long been of interest in
drug carriers and controlled release technology because
of the ability of these polymers to be reabsorbed by the
body [3]. This alleviates the need for removal, often sur-
gically, of a drug release device. The most widely used
and studied class of biodegradable polymers is the poly-
esters, including poly(lactic acid), poly(glycolic acid),
and their copolymers and poly(lactic acid) (henceforth
referred to as PLA) was investigated as a drug delivery
material as early as 1971 [3].
There are a large number of research groups, world-
wide, examining PLA in the form of microparticles and
nanoparticles, for use in controlled drug delivery systems
using a solvent evaporation technique, or modification
thereof [4,5]. Although these references, there isn’t any
work in literature which reports the preparation of star-
shaped PLA drug carrier nanoparticles.
In this work the synthesis of star-shaped PLA and the
preparation of nanoparticles using a modified solvent
evaporation method is reported.
2. Experimental Part
Star-shaped PLA was synthesized using dipentaerythritol
(DPE) as core, D,L-dilactide (LA) as monomer and Tin
(II) ethylhexanoate (Sn(Oct)2) as catalyst [6] as reported
in Scheme 1.
Monomer (5 g, 0.035 mol) was added under nitrogen
to a flame dried, 50 mL round-bottomed flask containing
a magnetic stir bar and sealed with a rubber septum. The
system was purged with nitrogen. Dipentaerythritol
(0.247 g, 0.00097 mol) in toluene (1 ml) was added via
syringe under nitrogen. The reaction flask was immersed
in a 130℃ oil bath and sufficient time was allowed for
the lactide and DPE to melt. A catalytic amount of
Sn(Oct)2 (0.162 g, 0.0004 mol) in toluene (1 ml) was
added, and the reaction mixture was allowed to stir for 10
min. The reaction temperature was decreased to 120℃,
and the reaction was allowed to proceed for 24 h. The
product was dissolved in chloroform, precipitated in a
hexane/methanol mixture (90:10), and dried in vacuo at
60℃ for 24 h.
Molecular weight and chemical structure of the
star-shaped PLA were analyzed by 1H-NMR. Nuclear
magnetic spectra, performed with a Bruker FT Avance
DPX200 instrument using CDCl3 as solvent and tetrame-
thylsilane as internal reference, is reported in the follow-
ing Figure 1.
Mn values was calculated by comparison of multiplet
at 5 ppm (a, 1H) with respect to the singolet at 4 ppm (e,

Preparation of Star-Shaped Polylactic Acid Drug Carrier Nanoparticles37
= DPE
O
O
O
O
HO
H2
C
CH2
OH
CH2
OH
H2
CO
H2
C
CH2
OH
CH2
OH
H2
COH
+
Sn(Oct)2
120 °C / N2
CH3
C
H
O
O
n
Where:
Scheme 1. Scheme of the synthesis of star-shaped PLA
a b
fd
c e
5
PPM
432
HO C
H c
CH
3
C
O
O
O
O
H
2
C
CH
2
OH
O
n
a
b
d
f
f
e
C
CH
2
OH
e
e
H
2
CC
H
2
Figure 1. 1H-NMR of the star-shaped PLA and relative signal assignment
12H). A good agreement between the calculated (~ 5450
g/mol) and the experimental (~ 5300 g/mol) molecular
weight was found.
In order to determine molecular weights and its distri-
bution gel permeation chromatography (GPC) using THF
as solvent at 30℃ was performed (relative Mark-How-
ink-Sakurada constants were used as reported in the lit-
erature [7]). A Waters instrument equipped by a Waters
1515 HPLC isocratic pump, a Mini-Mesopore (Polymer
Laboratories) 250 × 4.6 mm 5 μm column and Waters
2410 refractive index detector was used. Molecular
weights obtained from GPC (Mn and Mw of 4420 and
4810 respectively) are lower than the values calculated
by 1H-NMR, probably due to the star-shaped conforma-
tion of the macromolecules, which reduces dramatically
the hydrodynamic volume of the polymer. A very narrow
molecular weight distribution (a 1.101 of polydispersity
index) was achieved.
Once the star-shaped PLA polymers were synthesized,
the micelles nanoparticles were prepared by a solvent
evaporation method [4,5]. Practically, star-shaped PLA
was dissolved in ethyl acetate (10 mL) at the concentra-

Preparation of Star-Shaped Polylactic Acid Drug Carrier Nanoparticles 38
tions of 15% w/v. This polymer solution was preemulsi-
fied using a disperser (Ultraturrax T18 basic, IKA) at
8000 rpm for 5’ with 20 mL of an aqueous solution of
sodium dodecyl sulfate (2 g/L). Water (80 ml) was sub-
sequently added under magnetic stirring leading to the
nanoprecipitation of the polymer.
The morphology of nanoparticles was observed using
a JEOL JEM 2010 Transmission Electron Microscopy
(TEM) equipped with a GIF Gatan Multiscan Camera
and a microanalyzer EDS Inca 100. Photographs were
obtained using transmission microscope at an accelerat-
ing voltage of 200 kV. The sample was prepared by dip-
ping the TEM net in the previously described water solu-
tion. TEM micrographs of the PLA nanospheres are re-
ported in Figure 2.
As it is possible to see a very narrow distribution of
nanoparticles dimension was obtained, with an average
diameter of 15 ± 5 nm.
3. Conclusions
In this preliminary work, the synthesis of star-shaped
PLA and the preparation of nanoparticles using a modi-
Figure 2. TEM images (150KX) of the micelle-like star-shap-
ed PLA nanoparticles
fied solvent evaporation method is reported. The pre-
pared nanoparticles have average diameter of 15 nm,
much smaller than that of typical blood cells, such as
erythrocytes or lymphocytes (~7–10 μm), hence may be
injected into the bloodstream and used as drug carrier to
pass the blood brain barrier (BBB). In a second work the
efficiency of the nanoparticles as drug carriers will be
studied.
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