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Smart Dust: Nanostructured
microcarriers for drug delivery
Michael J. Sailor, Ph.D. Professor, UCSD Department of
Chemistry and Biochemistry [email protected]
William R. Freeman, M.D., Ph.D. Professor, UCSDDepartment of Ophthalmology
Lingyun Cheng, M.D.Assistant Project Scientist, UCSD
Department of Ophthalmology
Erkki Ruoslahti, M.D., Ph.D., The Burnham InstituteSangeeta N. Bhatia, M.D., Ph.D. Associate Professor, MIT
Department of Bioengineering
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2 technologies for controlled drug delivery to the eyeUnidirectional episcleral plaques use a nanostructured template to
prepare a polymeric material that can be sewn onto the back of the
eye. The plaque has a designed nanostructure that can be used tocontrol the rate of release of the drug.
Encoded microparticles use a
nanoporous Si or SiO2 material.
Methods to load, seal, and trigger
release of small molecule, peptide, or
protein-based drugs have been
developed.
nanotemplated
polymer
porous Si
master
composite
PLA
sclerananoporousmembranereservoirbacking
eyeinterior
Above: Photonic color
code changes when
particle releases payload.
Right: Porous Si micro-particles in the rabbit eye.
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Smart Dust photonic crystal particlesMichael J. Sailor, UCSD
Design a mother ship nanostructure to
carry and release a cargo or perform adiagnostic test
Build a code
Load a drug
Target the nanostructure to a desired
location
Monitor the nanostructure in-vivo
Ophthalmoscope image of porous Si photonic
crystals (green color) in the intravitreal region of
the rabbit eye. These particles are the size of the
diameter of a human hair. CourtesyWilliam R.
Freeman, M.D. and Lingyun Cheng, M.D., ShileyEye Center, University of California, San Diego
Smart Dust
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Porous Silicon Synthesis
Electron microscopeimage of porous Si.
Side view of porous Sielectrochemicallyetched into a single
crystal Si wafer.
Background:Properties of Porous Silicon; Canham, L.,Ed.; EMIS Datareviews, INSPEC: London, 1997; Vol. 18.
2Si + 6 HF + 2 h+
Si
H
Porous Si Surface
+ H2SiF6+ 2H
++ 1/2 H2
20 m
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Pore size is controlled electrochemically
Current Density for samples at right:
(A) 1.5 x 1.5 mm, 150 mA/cm
2
(B) 5 x 5 mm, 295 mA/cm2
(C) 5 x 5 mm2, 370 mA/cm2
(D) 5 x 5 mm2, 440 mA/cm2
(E) 5 x 5 mm, 515 mA/cm2
(F) 5 x 5 mm2, 600 mA/cm2
Depends on:
Current densityHF concentrationElectrolyte composition (usually
ethanol, but other organic solvents
have been used)
Dopant type, and dopantconcentration
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Range of Accessible Pore Sizes
1 0 0 0 n m = 1 m
1 0 0 n m
P o r o u s S i l i c o n P o r e S i z eB i o l o g i c a l M o l e c u
R e d b l o o d c e l l s
M i t o c h o n d r i a
H u m a n s e r u m a l b u m i n
D N A
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Photonic Crystals-color from a nanostructure
PARKER, A. R., et.al., J. Exper. Biol. 1998201, 1307-
1313.
Calloodes grayanus Porous Si multilayer
1
m
2 mm
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Berger, M. G.,et al., Thin Sol. Films1997, 297, 237-240Meade, S. O.;et al.Adv. Mater.2004, 16, 1811-1814.
Encoding strategy
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Complicated codes can be placed on a particle
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Microdroplet patterningto produce a composite photonic crystal
Li, Y. Y.; Kollengode, V. S.; Sailor, M. J.Adv. Mater.2005, in press.
silicon porousSiphotoniccrystal
etchspraypolymer
NaOH(aq)
250C30min
400 500 600 700 800 900 1000
Reflected
intensity(rel)
Wavelength (nm)
0 hr
1 hr
2 hr
3 hr
4 hr
5 hr
with polymerbare
Can encapsulate drugs,
attach targeting moieties
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Opening pores to load a drug
HF/DMSO
30 min
Dexamethasone
Langmuir2004, 20, 11264-11269.
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Chemistry can change rate of release of
dexamethasone from porous Si
0
20
40
60
80
100
120
0 1 2 3 4 5 6 7 8
%D
rugReleased
Time (hours)
Fresh
Hydrosilylated
H-terminated material
completely releases
dexamethasone after 2 hours,
corresponding to complete
dissolution of the porous Si
layer. After 7 hours only 50-60% of the drug is released
from the more stable
hydrosilylated material. After
an initial 2-hour burst, these
hydrosilylated samplessteadily released drug for a
period of 3 days.
Langmuir2004, 20, 11264-11269.
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Electropolished PSi Polymer-PSi Composite
Etching conditions : p++ Type Si wafer, HF:EtOH = 3:1 solution
100 mA/1.3 cm2 ~ 250 mA/1.3 cm2
2 sec intervals; 50 repeats
Electropolishing conditions: HF:EtOH = 1:14 solution
22 mA/1.3 cm2
2 min
In situ polymer. hydrolysis
Polymer-based
Photonic film
Polymer imprints from 1-D photonic crystals
Li, Y. Y. et al. Science299, 2045-2047 (2003).
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Porous Si/polynorbornene composite film held between
two pairs of tweezers, showing the mechanical stability of
the materials
Flexible 1-D photonic crystals
Yoon, et. al. Chem. Commun.2003, 680-68.
RingOpeningMetathesisPolymerization
PorousSi Template
Si
Si
Composite
400 500 600 700 800 900 1000
Relative
Intensity
Wavelength (nm)
Fresh Porous Si
Composite
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Monitoring drug delivery with a biocompatible
polymeric photonic crystal
0
0.01
0.02
0.03
0.04
0.05
0.06
10 100 1000
1100
1200
1300
1400
1500
1600
1700
Relativerugatep
eakintensity
Caffeine
abs
orbanceinsolution
Time, min
Measurement of degradation of polylactide rugate peak as a
surrogate for the delivery of caffeine (pH=10, aqueous)Li, et. al.
Science,2003 (299)2045-2047.
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Chemical Sensing with a Si Photonic Crystal
400 450500 550600 650700 750800
Wavelength(nm)
Si-R
R-Si
Si-R
R-Si
+A
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Targeted Microcarriers
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Silicon Porous Si Mirror Modified Porous Si
Double MirrorFreestandingPorous Si
Smart Dust
Etch Hydrosilylate
Etch
Release,oxidize
Sonicatehydrophilic
hydrophobic
hydrophobic
Self-orienting, self-targeting smart
dust particles
1-dodecene
J.R. Link and M.J. Sailor, Proc. Nat. Acad. Sci.2003, 100, 10607-10610.
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Encoded particles self-assemble on a target
oxidized
alkylated
Hydrophobic
Hydrophilic
Proc. Nat. Acad. Sci.2003, 100, 10607-10610.
S ti S t D t
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Superparamagnetic Smart Dust
Dorvee, J. R.; Derfus, A. M.; Bhatia, S. N.; Sailor, M. J. Nature Mater.2004, 3, 896-899.
silicon porousSiphotoniccrystal
modifiedporousSi
2-sidedphotoniccrystal
magneticamphiphilicparticles
Etch
1-dodecene
Etch
Release
Sonicate
alkylated
120C
InfuseFe3O4
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Smart dust chaperonesfor liquid droplets
500 600 700 800 900
ReflectedIntensity(rel)
Wavelength, nm
I
-
(aq)
Ag+
(aq)
AgI(s)
Spectral barcodes:
Nature Mater.2004, 3, 896-899.
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Porous photonic crystals with optical barcodes can be made that allow in-
vivo monitoring
Chemistry and electrochemistry allow control of loading, degradation, andrelease rates
Porous materials can be used as templates to produce biomaterials with
controlled pore size, porosity, and optical properties Preliminary animal studies show no irritation, toxic effects Targeting can be achieved by incorporation of magnetic domains or
homing molecules
Summary
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