[3] D. Marcano, et al. AcsNano. 2010, 4, 4806-4814. [4] A.Tavolaro, et al. 2013, submitted. [5] D. Depan, et al, Materials Science and Engineering C, (2011), ...
ABSTRACT
INTRODUCTION Doxorubicin hydrochloride (DOX), an anthracycline ring antibiotic, is a highly effective anti-neoplastic agent used in leukemia chemotherapy. However, the severe toxic sideeffects such as cardiotoxicity, alopecia, vomitting, leucopenia, and stomatitis have hampered the successful use of DOX [1]
Doxorubicin is one of the most famous drug to use for cancer treatment, but likewise one of the most lethal drugs in terms of side effects, the research aims to create an inorganic material- having a large surface area to make Nano carrier and then study its own properties. This work has utilized graphene oxide (GO) using modified Hummer’s method for obtaining improved colloidal suspensions of GO, that were dried to a room temperature producing flakes, and then it was carefully characterized and applied to Doxorubicin to test the adsorption process at different pH values.
Graphene, a new emergent nanomaterial with oneatom-thick, two-dimensional individual sheet structure composed of sp2 hybridized carbon atoms[2][3], due to chemical process it becomes an oxide graphene obtaining other physical properties[3], it has increasing attracted interest in the field of biological detection, drug delivery, and cancer therapies. It has extraordinary properties to develop new and eco-materials.
MATERIALS & METHODS Prepared synthesis of graphite oxide according to new Hummer’s method[3], which allows chemical modification from the original graphite to obtain the optimum product to test the adsorption and desorption properties. In this field there are some works that have been considered the carbon materials as nanocarriers in combination with other polymers[5].
The samples of graphene oxide and Doxorubicin were characterized by UVvis spectrophotometry (UV-160A spectrophotometer SHIMADZU), Fourier Transform Infrared ATR spectroscopy (Perkin Elmer Spectrum 100 FTIR spectrophotometer), and Scanning Electron Microscopy (SEM).
RESULTS & DISCUSSION
vibrations (3086,84 cm-1), C=O stretching, vibrations (1736,86 cm-1), epoxide characteristics (1041,59 -852,49 cm-1). DOX/GO nanohybrid at pH 7.7, the interactions of principal functional groups O-H correspond to hydroxyl group from 3113cm-1 to 3437 cm-1, showing a shifted to lower position in relation with initial DOX DOX/GO (pH 7,7)
The effects of contact time on adsorption of Doxorubicin with GO is showed in Figure 5. It can be observed that the adsorption is very slow, so in the first 10 min approximately 8%, the percentage removal increased from 30% to 60%, and the adsorption continuously increases until to 24h at pH 7.7. However, the capacity adsorption at acidic conditions was better than neutral conditions, this fact was verifiable due to the different degrees of hydrogen-bonding interaction between these two species under different pH conditions. a)
b)
% Adsorption in 20ug/ml % Adsorption in 50ug/ml % Adsorption in 100ug/ml % Adsorption in 200ug/ml
100
% Adsorption in 20ug/ml % Adsorption in 50ug/ml % Adsorption in 100ug/ml % Adsorption in 200ug/ml
100
80 80
% ADSORPTION pH 3
the UV-vis of DOX at pH 7.7 showed two characteristic peaks, one at 240 nm in the transition of aromatic groups, other at 487 nm, then last is the characteristic peak of drug. [6]
FTIR-ATR spectra show for DOX the principal functional groups, O–H stretching vibrations ( 3414,62 cm-1), C-H stretching vibrations (2924,84 cm-1), C=O stretching vibrations (1723,85cm-1), primary amine NH2 wagging (871,86cm-1). GO shows O–H stretching
% ADSORPTION pH 7
The UV-vis analysis of graphene oxide aqueous suspension is shown in the figure 3. and it revealed the * transitions (conjugation), characterized by a absorbance peak around 224 nm that results to be comparable with the literature data [3]. The kinetic of adsorption reveals that this process increases by the time contact is increasing,
60
40
20
60
40
20
1773,93 2300,90 2893,88 3437,82 3369,80 3113,78
1646,89
1258,87
2841,88
0 0
1115,72 861,71 817,72
5
10
15
CONTACT TIME (h)
948,65
20
25
0 0
5
10
15
20
25
CONTACT TIME (h)
1053,58 1460,95 1381,96
1627,91
666,94
GO
1736,86
3086,85 2957,84 2928,83 2858,86
%T
1243,97
975,59 1041,72 853,67
2026,86 1723,84
1515,85 1444,82
2919,83 1637,75
1584,80
1284,81
1116,83 986,81 1085,83 1212,82 1014,81
871,86 723,86 819,85 688,86 793,85 763,85
3548,66 1409,82
DOX (pH 7,7)
1618,72 3474,59
4000.0
RESULTS DISCUSSION For the Kinetic analysis, various drug concentrations at pH 7.7 were used. In a typical experiment, 20 ug/ml, 50ug/ml, 100 ug/ml, 200 ug/ml solutions tested with 1mg GO solid until 24h. A comparison of the drug adsorption by using different pH concentrations (figure 6) reveals that this process is favored in acid conditions.
Amount of adsorption at pH 7,7 Amount of adsorption at pH 3
AMOUNT OF ADSORPTION (ug/mg)
350
300
250
200
150
100
50
0 0
20
40
60
80
100
120
140
160
CONCENTRATION OF DOX (ug/ml)
180
200
220
3600
3200
2800
2400
2000
1800 cm-1
1600
1400
1200
1000
800
650.0
SUMMARY DOX adsorption performance on GO was investigated by using the depletion method varying the incubation time, drug concentration and the pH values. The adsorption percentage of the drug at pH 7.7 was observed to be higher (equal to 100 %) than that obtained at acidic pH 3 (85%). To refers the results by FTIRATR analysis indicate that π-π stacking interactions exist among inorganic material and DOX. This result confirms that GO is a very interesting nanomaterial for nanomedicine applications.
CONCLUSION In this work we studied the efficiency of adsorption of synthetic GO material. The obtained results with Doxorubicin are satisfactory, because percent of adsorption was high (approximately to 100 %). Actually, this investigation is carried out later 24h at different contact time by using various concentrations of drug solutions: the next step is to prepare novel membranes to test its efficiency on GO in this process.
REFERENCES [1] S. Wu, et al. Materials 2013, 6, 2026-2042 [2] A.K. Geim, K.S. Novoselov, Nat. Mater. (2007) 6, pp 183–191. [3] D. Marcano, et al. AcsNano. 2010, 4, 4806-4814. [4] A.Tavolaro, et al. 2013, submitted. [5] D. Depan, et al, Materials Science and Engineering C, (2011), pp 1305–1312 [6] X. Yang, et al, J. Phys. Chem,( ACS publications, Washington DC, 2008, 112 (45), pp 17554–17558
