1. 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***
* 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

2. 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

3. Encapsulation Nanocapsules as containers Nanospheres as matricesnm
- protection of the drug
- vectorisation toward the target
- control of drug release

4. 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  stable emulsion
Dilution with distilled water
 Diffusion of the solvent
 Drops  capsules i.e. core:oil + drug+ polymer membrane around the core

5. Preparation of nanocapsules
Oil + drug +
Polymer
Oil + polymer + solvent
+ drug
solvent
DROP 1 mm
CAPSULE  500 nm
external phase: saturated water + sabilizer
external phase: distilled water + stabilizer

6. TEM study of the nanocapsules: negativation method

7. TEM size distribution measurements

8. Positive TEM observations Direct deposition of the NC on the carbon gride
200 nm
100 nm
The NC membrane can be estimated from to the dark halo due to the stabilizer
Image of a broken NC ( during TEM observation) revealing the oil content. A halo of liquid expands around the NC on the carbon film

9. Positive TEM observations
Spongeous structure inside the NC

10. Crystallization of polymer inside the NC
Monocrystal
polymer
capsule
Polycrystalline
sponge
polymer inside
the capsule

11. Micro- capsules SEM image
The black points on the capsule surface are holes connecing the internal pores to the surface
TEM images

12. 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.

13. Spongeous polymer nanocapsule