SYNTHESIS OF A NANOSTRUCTURED SILICA DEVISE USE IN THE CONTROLLED

DRUG DELIVERY OF DOPAMINE IN THE CENTRAL NERVOUS SYSTEM

T. López , D. Esquivel , N. Plascencia , P. Quintana and R. D. González
1,2 3 4 5 6

Nanotechnology Materials Laboratory . UAM, Mexico D. F.; National Institute of Neurology and Neurosurgery “MVS” México.D.F. 3Universidad de Guanajuato, CIQI.
1,2

México 4 “20 de Noviembre”, I.S.S.S.T.E. México 5 CINVESTAV-IPN-Mérida,Yucatán, México 6 Tulane University, New Orleans

ABSTRACT INTRODUCTION
In the systemic treatment of Parkinson’s disease, L-dopa has been the drug of choice. This is The sol-gel technique is based on the phase transformation of a sol to gel, the sol is obtained by the
due to the instability of dopamine which is rapidly oxidized to the corresponding quinone in the hydrolisis of a organosilicates and gel is obtained by the policonsation of the hydirlized organosilicates.
central nervous system. In this study, we describe our efforts to stabilize dopamine by Silica sol-gel can be used as drug controlled release device due to the exceptional biocompatibility,
encapsulating it within a nanostructured silica device which can be directly implanted into the
brain using stereotaxic surgery. The surface properties of this device are closely related to rate at
morphological, chemical ,mechanical properties and the mild condition synthesis . The incorporation of
which dopamine can be released. Characterization studies have been performed using standard the drug in the SiO2 network was carried out at different sol-gel synthesis parameters: ethanol/alcoxide,
physical methods, which include Uv-vis, BET, SEM, as a function of dopamine concentration water /alkoxide ratio and dopamine concentration. The influence of this sol-gel synthesis parameters on
within the device. In particular, the rate of drug release was found to be strongly dependent on the pore structure, BET surface area and pore size distribution was investigated. Different properties of
the H2O/ETOH/TEOS ratio and dopamine concentration used in the sol-gel synthesis of the pores will directly affect the drug diffusion through the matrix and consequently the drug release
material. The behavior of dopamine and dopaminequinone adsorbed on silica can be tailored to kinetics
obtain the desired rate of release. The drug release kinetics will be discussed during this
presentation.

pore size distribution variaying dopamine concentration 0 with out ethanol

pore size distribution 5 mol ethanol variaying water concetration Pore size distribution variaying dopamine concentration 5 mol ethanol
1.6
3 1.5
2.0
1.4
1.3
SD1551 1.2
1.5 SD11551 1.1 SD1451
SD1101 SD1251 1.0 SD14517
dV/dLog D cm /g
2
SD12551
3

SD1401

dV/dLog D cm /g
0.9 SD14525
dV/dLogD cm /g

3
SD14025 SD1351
3

1.0 0.8 SD1455

SD1405 SD13551
0.7 SD14575

RESULTS
SD14075 SD1451
0.6
SD14010
0.5 0.5
1
0.4
0.3
0.0 0.2
0.1
0 200 400 600 800 1000 1200 1400 1600 0.0

Textural Analysis 0
0 200 400 600 800 1000 1200 1400 pore size A
-0.1

0 200 400 600 800 1000 1200

pore size A
pore size A

BET Mean
SAMPLE TEOS water Ethan %w
surface pore
S mol mol ol Dop. area diameter
m2/gr Å
550
DOP/SiO2 Isotherms: Dopamine concentration effect.
silica isotherms 0 mol ethanol variaying dopamine concentration
PREPAR mol 1800 1800 isotherms variaying water concentration 5 mol ethanol
500
10 450
750

ED 1600
600 1600
SD1101
700
650
SD1551
SD1151
400
SD1451
SD14517
1400 1400 SD1401 8
600 SD14525
SD1155 350
75 224 SD14025 550 SD1251 SD1455

vol.ads. cm /g
SD1101 1 10 0 10
1200 1200 SD1405 300 SD14575

3
400 500 SD1255
SD14075 450 SD1351
1000 1000 6 250
sd14010
vol. ads. cm /g

vol.ads. cm /g

400 SD1355
3
3

100 170 800 800

350 SD1451 200

SD1401 1 40 0 10 200
600 600
300
4
250 150
200
150 100

620 147 400 400

100
SD14025 1 40 0 25 0
200 200
2
50
0
50

0
-50 0.0 0.2 0.4 0.6 0.8 1.0

172 101
0 0
0
-100 o
P/P
SD1405 1 40 0 50 -200
0.0 0.2 0.4 0.6 0.8 1.0
-200
0.0 0.2 0.4 0.6 0.8 1.0
0 0.0 2 0.2 40.4

P/P
o
0.66 0.8 8 1.0 10

o o

136 124 P/P P/P

CONCLUTIONS
SD14075 1 40 0 7.5
76 122
SD14010 1 40 0 100 Diffuse reflectance IR
290 63
SD1551 1 5 5 10
Sílice
420 66 120
SD1401
SD1151 1 10 5 10 110
SD14025
SD14075
SD14010

The synthesis parameters affect:

100

445 56
SD1101

SD11551 1 15 5 10 90
% reflectance

80

418 67 70

SD1251 1 20 5 10 60
• The mean pore diameter
• Specific surface area
50

296 91
SD12551 1 25 5 10 40

30
• Hysteresis loop
317 93 4000 3500 3000 2500 2000 1500 1000 500

SD1351 1 30 5 10 cm
-1

SD1551
SD1151

361 88 SD1251
SD12551

SD13551 1 35 5 10 SD1351
SD13551
SiO2

100
115 177
SD1451 1 40 5 10
% de reflectance

92 182
SD14517 1 40 5 17.5
50

288 105
SD14525 1 40 5 25
182 82
SD1455 1 40 5 50 4000 3000 2000 1000
-1
cm
103 95
SD14575 1 40 5 75