Transcript TEM and SEM studies on nano- and micro

TEM and SEM studies on nano- and
micro-capsules from biodegradable
polymers for drug encapsulation
• V.S. Teodorescu*, M.G. Blanchin**,
• S. Guinebretière***, S. Briançon***, H. Fessi***
•
•
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* INCDFM, Bucharest-Magurele, ROMANIA
**Laboratoire de Physique de la Matière Condensée et
Nanostructures,
Université Claude Bernard Lyon
1,Villeurbanne, FRANCE
***Laboratoire d ’Automatique et de Génie des Procédés,
Université Claude Bernard Lyon 1,Villeurbanne, FRANCE
Vectorisation , encapsulaion,
electron microscopy TEM and SEM
•Polymeric capsules are increasingly used as vectors for applications
in chemistry, pharmacy, cosmetics…
•Pharmaceutical applications for intravenous vectorisation require
capsule sizes down to the nanometer range
•SEM and also TEM should be used to study of the structure and the
morphology of nano- and micro-capsules
Encapsulation
Nanocapsules
as containers
Nanospheres
as matrices
10 - 1000 nm
- protection of the drug
- vectorisation toward the target
- control of drug release
Preparation of nanocapsules

Water and solvent partially miscibles (ethyl acetate)
 Polymer : soluble in solvent, insoluble in water (biodegradable polyesters /
e.g. poly-e-caprolactone PCL)
 Oil :miscible with polymer solution, dissolves the drug (triglycerides)

Tensio active compound as stabilizer in the aqueous phase (PVA, copolymer)

Water and solvent initially saturated 

Dilution with distilled water
stable emulsion
 Diffusion of the solvent
 Drops  capsules i.e. core:oil + drug+ polymer membrane around the core
Preparation of nanocapsules
Oil + polymer + solvent
+ drug
Oil + drug +
Polymer
solvent
DROP 1 mm
external phase:
saturated water
+ sabilizer
CAPSULE  500 nm
external phase:
distilled water
+ stabilizer
TEM study of the nanocapsules: negativation method
Capsule
Polymer
negativated
film
Carbon
film on the
grid
50 nm
Sketch
of the
contrast
in the
TEM
image
TEM size distribution measurements
Sphere diameter distribution
1 µm
20
N
15
10
5
0
1
2
3
4
5
6
7
8
D (x100 nm )
9
10 11 12
Positive TEM observations
Direct deposition of the NC on the carbon gride
200 nm
100 nm
Image of a broken NC ( during TEM
observation) revealing the oil
content. A halo of liquid expands
around the NC on the carbon film
The NC membrane can be
estimated from to the dark halo due
to the stabilizer
Positive TEM observations
Spongeous structure inside the NC
Crystallization of polymer inside the NC
Monocrystal
polymer
capsule
Polycrystalline
sponge
polymer inside
the capsule
Micro- capsules
SEM image
The black points on the capsule
surface are holes connecing
the internal pores to the
surface
TEM images
CONCLUSIONS
 TEM structural and morphological study of polymeric
NC for drug encapsulation can be made using the classic
negativation method, but also by direct observations
 Direct deposition of the NC on the TEM grids provides
data about all the components of the NC
 The polymeric membrane of the NC can be resolved using
TEM direct observation
TEM observations are complementary to the SEM images
in the case of capsules in the range of 1 to 10 mm.
Spongeous polymer nanocapsule