Journal of Electron Spectroscopy and Related Phenomena 181 (2010) 181–185
Contents lists available at ScienceDirect
Journal of Electron Spectroscopy and
Related Phenomena
journal homepage: www.elsevier.com/locate/elspec
Photophysical characterization of cumarin-doped poly (lactic acid)
microparticles and visualization of the biodistribution
Shigeaki Abe
a,∗
, Takayuki Kiba
b
, Kiyotada Hosokawa
b
, Satoru Nitobe
b
, Takashi Hirota
b
,
Hirohisa Kobayashi
b
, Tsukasa Akasaka
a
, Motohiro Uo
a
, Yoshinori Kuboki
a
,
Shin-Ichiro Sato
b
, Fumio Watari
a
, Iosif D. Rosca
c
a
Department of Biomedical Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, Kita 13, Nishi 7, Sapporo 060-8586, Japan
b
Division of Biotechnology and Macromolecular Chemistry, Graduate School of Hokkaido University, Sapporo 060-8628, Japan
c
Faculty of Engineering and Computer Science, Concordia University, 1455 de Maisonneuve Blvd. W, Montreal, QC H3G 1M8, Canada
article info
Article history:
Available online 24 May 2010
Keywords:
Microscopic environment
Solvation effect
Biodistribution
Controlled drug release
Biodegradable polymer
abstract
We prepared fluorescent coumarin dye-doped poly (acrylic acid) microparticles, which are well known
as a biodegradable polyester, and the photophysical properties were characterized by scanning electron
microscope, atomic force microscope and spectroscopic investigation. Spherical particles with diameters
ranging from 0.5 to a few m were obtained. Based on spectroscopic investigation, the internal envi-
ronment was close to that of a polar solvent such as methanol, and the dyes were dispersed without
aggregation inside the particles. The obtained particles were administered to a mouse through the tail
vein, and the biodistribution was then observed after some organs were excited at 1-day and 1-week
post-injection. The particles were accumulated in the organs, especially in the lung and spleen. After
injection, the particles were trapped temporally in the lung, and then seemed to be transported to other
organs by blood circulation. This tendency is similar to the biodistribution of TiO
2
microparticles that we
have reported previously.
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
Recently, several kinds of polymers have gained attention due to
their potential application to medical science and tissue engineer-
ing; their physical, chemical, and mechanical properties appear
to be suitable for industrial and medical applications. Poly (lactic
acid) (PLA) and poly (lactic acid-co-glycolic acid) (PLGA), a typi-
cal polyester and its co-polymer, are widely used as biomaterials
[1–4]. These polyesters are well known to have a low immuno-
genicity and toxicity, and excellent biocompatibility. Their lack of
chemical functionalities to elicit specific cell or tissue interactions
is considered to be a desirable property for biomaterials. They are
also easily biodegraded. Therefore, many researchers have inves-
tigated their potential for use in bone fixation [5], surgical sutures
[6], controlled drug release [7–9], and composite formation with
collagen, hydroxyapatite, or carbon nanotubes [10–12].
A controlled drug-release system [13–15] is one of the desired
applications for biodegradable polymer. Conventional oral drug
administration normally works in an uncontrolled manner. There-
fore, the drug has an effect at the therapeutic level for only a
∗
Corresponding author. Tel.: +81 11 706 4251; fax: +81 11 706 4251.
E-mail address: sabe@den.hokudai.ac.jp (S. Abe).
short time. As such, multiple drug administration is necessary,
which can lead to other problems such as side effects because of
over-adoption. For an effective controlled release system, an encap-
sulated matrix must be developed to protect the drug agent. The
matrix would be transported to target organs, and the drug would
then be effectively released during a controlled time period. Drug
administration can therefore be minimized, which can reduce the
risk of side effects. The system is expected to useful for the selec-
tive administration of anti-cancer agents and gene transfection to
the desired organs. For the development of these systems, it is nec-
essary to investigate not only the controlled release but also the
biodistribution of these materials. In addition, it is necessary to elu-
cidate the biodistribution from the perspective of the assessment
of nanotoxicology. When the particle size reaches the micro-/nano-
level, some of them show toxicity in vitro, even when they are
considered biocompatible at the macro level [16–18]. However, it
is not enough to clarify the biocompatibility and/or nanotoxicity of
micro-/nano-sized materials and the distribution in body.
In this study, we have attempted to estimate the biodistri-
bution of the micro-sized polyester particles. For this purpose,
we have prepared micro-sized PLA particles containing coumarin-
6, which is a typical fluorescent dye, as a model material of
drug-encapsulation particles. We also attempted to determine the
internal environment of the particles by spectroscopic investiga-
0368-2048/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.elspec.2010.04.002