Date of Award

Fall 2005

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering

First Advisor

Yuri Lvov

Abstract

In this study, we applied the traditional Electrostatic layer-by-layer (ELBL) assembly procedure to fabricate nanothin films over flat surfaces, and modify particle surfaces to influence the drug particle size, and drug release. The ELBL assembly has previously been applied to fabricate multilayer nano-scale thin films, but its ability to instantaneously influencing particle size is unique. Other unique observations such as influence on drug release as a result of polymer complexation, and thermal changes occurring during layer fabrication are recorded.

The ELBL self-assembly process was applied to produce dexamethasone particles layered with various polyelectrolyte layer combinations. These combinations were further applied to modify insulin (PROMAXX®) particles. The protein based PROMAXX®particles were primarily modified to impart stealth and controlled release properties. The nanothin shells were characterized by quartz crystal microbalance measurements for layer assembly and thickness, microelectrophoresis for surface charge, microcalorimetry for thermal activity of assembly process, confocal microscopy, and scanning electron microscopy for visual conformation of layer assembly.

In-vitro release profiles of dexamethasone nanocapsules suspended in water or carboxymethylcellulose gels were measured using vertical Franz-type diffusion cells in conjunction with U--V Spectrophotometer.

Sonication of a suspension of dexamethasone microcrystals in a solution of PDDA not only reduced aggregation but also influenced particle size. Assembly of multiple polyelectrolyte layers around these monodispersed cores produced a polyelectrolyte multilayer shell around the drug microcrystals allowing controlled release depending on the composition and the number of layers. Thus, direct surface modification of dexamethasone microcrystals via the ELBL process produced submicron particles with diffusion controlled sustained drug release through the polyelectrolyte multilayer shell.

An interesting observation was made with the assembly of polyelectrolyte layers around the insulin particles (PROMAXX®). Through the process of complexation each alternate fabricated layer strengthened or weakened the layer interactions with the drug surface leading to slower or faster release rates.

Preliminary testing of a new approach for layer and particle assembly on flat solid substrates using an electrohydrodynamic atomizer was successfully demonstrated. Pre-labeled sub micron drug particles appeared to be assembled over the flat substrate modified by alternate layers of polyelectrolytes.

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