• 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