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

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  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 Oil + drug + Polymer Oil + polymer + solvent + drug solvent DROP 1 mm CAPSULE  500 nm external phase: saturated water + sabilizer external phase: distilled water + stabilizer

TEM study of the nanocapsules: negativation method

TEM size distribution measurements

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

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