Iodine POLY(EPSILON-CAPROLACTONE) CONJUGATE WITH

TETRACYCLINE, A POSSIBLE MATRIX FOR DRUG

DELIVERING SYSTEM.
Lidiane G. da Silva1, Maria E. Leyva1,Élcio R. Barrak1, Daniela Sachs1, Alvaro A. A. de
Queiroz1.
1- Centro de Investigação e Inovação de Materiais Funcionais Avançados, Universidade Federal de Itajubá - UNIFEI,
Itajubá – MG
E-mail: g.lidiane@yahoo.com.br

Resumo. The poly(ε-caprolactone) (PCL) and their copolymers, are used as biomaterial for tissue
engineering and drug delivery system. PCL was synthesized by change transfer complex method using
iodine as initiation for the group of bioactive polymers and biomimetic at UNIFEI (PCL) (ARRUDA,
QUEIROZ e HIGA, 2003). In this context, conjugates of PCL with tetracycline (PCL/Tr) was made and
caracterizated investigating its properties that can be used for release of drugs. PCL and PCL/Tr was
characterized by Differential Scanning Calorimetry (DSC) using a Perkin Elmer DSC60,
Termogravimetric (TGA) using a Metler thermogravimetric analyzer at a heating rate of 10 oC/min under
oxigen atmosphere and Fourier Transform Infrared (FTIR) spectroscopy in a Perkin Elmer Spectrum-100
spectrometer. The conjugate was prepared by dissolving the Tr and PCL in chloroform to obtain
homogeneous solution, when stirred with a magnetic stirrer at room temperature. The petri dish
containing the conjugate solution was then lyophilized. The FTIR spectra of PCL/Tr shows strong of the
carbonyl stretching mode around 1705,05 cm−1, 1614 cm-1 corresponding to carbonily group at aromatic
ring and 1582,06 cm-1 corresponding to N-H bending proving that Tr was associated with I-PCL. The
PCL/Tr exhibited fusion temperature of a 60,90°C and fusion enthalpy 84,81 J.g -1, exhibiting no
significant changes compering to PCL-I . The TGA showed that PCL-I and PCL/Tr had a similar weigth
loss. Acording to FTIR spectra of PCL/Tr there was a success association between Tr and PCL, the DCS
and TGA analisys showed that conjugate had no significant changes in melting point and similar weigth
loss comparing to PCL. These results indicated that the conjugate can be good candidate for drug
delivering system and will be futer topic to next step of this research.

Palavras-chave: Poly(ε-caprolactone), Drug release, Tetracycline.

1. INTRODUCTION

The development of bioresorbable polymers pharmacologically active presents

major advances in clinical practice since the surgical procedures provide a high risk of
infection, inflammation and pain. In recent years, biodegradable and bioreabsorbable
polymers are widely investigated for applications in biomedical fields. Actually, most of
the commercially available biodegradable devices composed of homopolymers or
copolymers of glycolides, lactides and -caprolactone.
Poly(-caprolactone) (PCL) , an aliphatic polyester synthesized from -
caprolactone is biocompatible and biodegradable aliphatic polyester that is
bioresorbable and non-toxic for human body. Because of its unique combination of
biocompatibility, permeability, and biodegradability, PCL has been widely applied in
medicine as artificial skin, artificial bone, and containers for sustained drug release
(WOODRUFF and HUTMACHER, 2010).
 The specific objective of this work is to study the in vitro release kinetics of the
polymer PCL-UNIFEI and demonstrate that this material can be used as a system of
drug release.

2. EXPERIMENTAL

2.1 MATERIALS AND METHODS

The PCL conjugates were made by using solvent evaporation method. The
conjugate was prepared by dissolving the Tr and PCL in chloroform to obtain
homogeneous solution, when stirred with a magnetic stirrer at room temperature. The
petri dish containing the conjugate solution was then lyophilized. FTIR spectra were
recorded on Fourier-transform infrared (FT-IR) spectrometer Perkin Elmer Spectrum
100 Series. The melting point and the enthalpy of fusion of the polymer were
determined by differential scanning calorimetric (DSC) measurements using a thermal
analyzer Shimadzu DSC-60 at a heating rate of 10°C/min and Termogravimetric
(TGA) using a Metler thermogravimetric analyzer at a heating rate of 10 oC/min under
oxigen atmosphere.

2.2 RESULTS AND DISCUSSION

The conjugate PCL, tetracycline (Tr) and PCL/Tr was characterized by FT-IR
spectrometer as showed in figure1.
Figure 1- FT-IR spectra of PCL, PCL/Tr and Tr. (A) PCL; (B) The absorption band at
1614cm-1 and 1228cm-1 suffered a significant decrease in intensity and shift.; (C) The
absorption bands around 1045 cm-1, 107 cm-1, 1120 cm-1 and 1100 -1300 cm-1 are
characteristic of C-O, C-O-O and phenolic hydrogen bonds respectively. Absorption
bands aurond 2500cm-1 and 3500cm-1 corresponding to νCH, νOH and νNH
respectively. Carbonila band corresponding to 1614cm-1 and 1228cm-1 corresponding to
C-N bound.

The FTIR spectrum absorption bands of Tr fig.1 (C) at 1045, 1075 and 1120 cm-
1
, characteristic of the vibration of CO bonds COC linkages of tetracycline (LEYPOLD,
-1
Reiher, et al., 2003). The region around 1100 cm and 1300 cm-1 corresponds to the
vibration of the phenolic hydrogen (BARTZATT, Koziol and Stoddard, 2001). The
absorption band between 2500 cm -1 and 3500 cm-1 corresponding to the vibrations of
the CH groups CH, OH e NH respectively. The absorption band at 1614 cm-1
corresponding to vibration of carbonyl group (C = O) and the band at 1228 cm-1
corresponds to the vibration CN () (OBALEYE, and Adeyemi Balogun, 2001).
It can be seen that the absorption band at 3299 cm -1 is absent in the PCL-Tr fig.1 (B)
and the bands 1614 cm-1 and 1228 cm-1 experienced a significant decrease in the
intensity and displacement suggesting partial interaction between Tr and the PCL's
probably for the formation of hydrogen bonds.
 Termogravimetric curves of PCL/Tr, PCL and Tr
100

PCL/Tr
80 PCL
Tr
Mass (%)

60

40

20

0
100 200 300 400 500 600
Temperature (°C)

Figure 2- Termogravimetric curves of PCL/Tr, PCL and Tr. The mass loss start
at 250°C in PCL/Tr corresponding to Tr starts of mass loss.

It is observed at fig.2 that the temperature of 250 ° C occurs a decrease in mass

temperature which marks the start of degradation of the drug and carbides formed Tr
(Unger, SIESLER and Vogel, 2010). Comparing loss weight of PCL and PCL/Tr there
was no significant changes in curves showing a good accession of Tr to PCL.
 DSC curve of PCL,Tr and PCL/Tr
60
PCL/Tr
PCL
Tr

Heat Flow (mW)

ENDO

30

40 80 120 160 200 240 280 320 360 400 440 480 520 560 600

Temperature(°C)

Figure 3- Differential scanning calorimetry of PCL, PCL/Tr and Tr. The fusion
temperature of PCL/Tr was around 60°C just like PCL.

Figure 3 shows DSC curves comparing PCL, PCL/Tr and Tr. It can be observed that
there was no changing of melting point for PCL/Tr comparing to PCL keeping melting
characteristics of PCL.
CONCLUSION
According to FT-IR spectra’s can be observed that there was a good adhesion
of Tr to PCL. DSC and TGA curves showed that the melting point and weight loss of
PCL comparing with PCL/Tr had no significant changes. In conclusion, PCL can be a
good matrix for drug delivering systems observing that this association have no changes
in physical properties then this material, ie, this material continues to have its
fundamental properties and medical applications.

ACKNOWLEDGEMENTS

This work was supported by Finep, CNPq, Fapemig and Capes.

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