v.s. teodorescu*, m.g. blanchin**, s. guinebretière***, s. briançon***, h. fessi*** * incdfm,...
TRANSCRIPT
• 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
TEM and SEM studies on nano- and micro-capsules from biodegradable
polymers for drug encapsulation
•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
Vectorisation , encapsulaion,
electron microscopy TEM and SEM
Vectorisation , encapsulaion,
electron microscopy TEM and SEM
Encapsulation
Nanocapsules as containers
Nanospheresas matrices
10 - 1000 nm
- protection of the drug
- vectorisation toward the target
- control of drug release
- 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--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
Preparation of nanocapsules
DROP 1 m CAPSULE 500 nm
Oil + polymer + solvent+ drug
solvent
Oil + drug +Polymer
external phase: saturated water + sabilizer
external phase: saturated water + sabilizer
external phase: distilled water + stabilizer
external phase: distilled water + stabilizer
TEM study of the nanocapsules: negativation method
Polymernegativatedfilm
Carbonfilm on thegrid
Capsule
Sketchof thecontrastin theTEMimage
50 nm
TEM size distribution measurements
Sphere diameter distribution
0
5
10
15
20
1 2 3 4 5 6 7 8 9 10 11 12
D (x100 nm)N
1 µm
Positive TEM observationsDirect deposition of the NC on the carbon gride
100 nm200 nm
The NC membrane can be estimated from to the dark halo due
to the stabilizer
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
Image of a broken NC ( during TEM observation) revealing the oil
content. A halo of liquid expands around the NC on the carbon film
Positive TEM observations
Spongeous structure inside the NC Spongeous structure inside the NC
Crystallization of polymer inside the NC
Monocrystal
polymer
capsule
Monocrystal
polymer
capsule
Polycrystalline
sponge
polymer inside
the capsule
Polycrystalline
sponge
polymer inside
the capsule
Micro- capsules
SEM imageSEM image
TEM imagesTEM images
The black points on the capsule surface are holes connecing the internal pores to the surface
The black points on the capsule surface are holes connecing the internal pores to the surface
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 m.
CONCLUSIONS CONCLUSIONS
Spongeous polymer nanocapsule