Controlled Release of Dexamethasone from Microcapsules Produced by Polyelectrolyte Layer-by-Layer Nanoassembly

Pharmaceutical Research, Vol. 22, No. 5, May 2005 ( 2005)

DOI: 10.1007/s11095-005-2600-0Research PaperControlled Release of Dexamethasone from Microcapsules Produced by

Polyelectrolyte Layer-by-Layer NanoassemblyNikhil Pargaonkar,1 Yuri M. Lvov,1 Ning Li,2 Jan H. Steenekamp,3 and Melgardt M. de Villiers2,4Received November 20, 2004; accepted January 28, 2005Purpose. In an effort to expand the application of core-shell structures fabricated by electrostatic

layer-by-layer (LbL) self-assembling for drug delivery, this study reports the controlled release of

dexamethasone from microcrystals encapsulated with a polyelectrolyte shell.Methods. The LbL self-assembly process was used to produce dexamethasone particles encapsulated

with up to five double layers formed by alternating the adsorption of positively charged poly(dimethyldiallyl ammonium chloride), negatively charged sodium poly(styrenesulfonate) and depending on the

pH positively or negatively charged gelatin A or B onto the surface of the negatively charged dexamethasone particles. The nano-thin shells were characterized by quartz crystal microbalance measurements, microelectrophoresis, microcalorimetry, confocal microscopy, and scanning electron microscopy.

In vitro release of dexamethasone from the microcapsules suspended in water or carboxymethylcellulose

gels were measured using vertical Franz-type diffusion cells.Results. Sonication of a suspension of negatively charged dexamethasone microcrystals in a solution of

PDDA not only reduced aggregation but also reduced the size of the sub-micrometer particles. Assembly of multiple polyelectrolyte layers around these monodispersed cores produced a polyelectrolyte

multilayer shell around the drug microcrystals that allowed for controlled release depending on the

composition and the number of layers.Conclusions. Direct surface modification of dexamethasone microcrystals via the LbL process produced

monodispersed suspensions with diffusion-controlled sustained drug release via the polyelectrolyte multilayer shell.KEY WORDS: controlled release; dexamethasone; layer-by-layer; microcapsules; polyelectrolytes.INTRODUCTIONRecently, a layer-by-layer (LbL) self-assembly for preparing ultra-thin films based on the electrostatic attraction

(15) between oppositely charged polyions began to receive

attention for its application in drug delivery (611). In this

method, the spontaneous sequential adsorption of dissolved

anionic and cationic polyelectrolytes, depending on the

charge of the substrate, leads to the formation of ordered

multilayer assemblies on the solid substrate surface (2,1215).

The reversal of surface charge after each immersion is the

crucial factor for a stepwise growth of the multilayer films by

this electrostatic LbL self-assembling process (16). Unlike liposomes, polyelectrolyte multilayer microcapsules are tough

and homogenous (6). Templates such as organic and inorganic colloid particles can be coated and the templates then