(577c) Incorporation of Various Forms of Dexamethasone Acetate Into Biodegradable Nanoparticles with Encapsulated Magnetite

Steroids have been reported to be effective for the treatment of sensorineural hearing loss. Dexamethasone (DEX) is one of the corticosteroids which have shown hair cell protection in previous studies. The majority of current treatments using corticosteroids involve middle ear direct injection which has limited inner ear distribution and it is hard to maintain drug levels over an extended period of time. Clearance from the middle ear is another problem. Poly(lactic-co-glycolic acid) polymeric nanoparticles encapsulating dexamethasone might represent a way to deliver corticosteroids to inner ear and to release therapeutics locally in a controlled and sustained manner. In this study, we tested three forms of dexamethasone: the basic form, the phosphate form and the acetate form for efficiency of encapsulation as well as release profile. With the water-soluble phosphate form, a water-oil-water double emulsion process was used, while with the two other forms, an oil-in-water procedure was used. The most hydrophobic of these forms, the dexamethasone acetate, yielded the highest encapsulation efficiency as well as minimal burst release followed by a slow, steady release over many days. The incorporation of oleic acid coated superparamagnetic magnetite nanoparticles (size ~10 nm) did not change either the amount encapsulated or release profile. The magnetite is well dispersed and the PLGA particle size/shape and surface charge does not change dramatically with magnetite encapsulation.