The effect of polymer composition and polymerization parameters such as comonomers, crosslinking ratio, and polymerization method, on the surface characteristics, surface chemistry, and swelling response of crosslinked 2-(diethylaminoethyl methacrylate) (DEAEM) and polyethylene glycol monoethyl ether monomethacrylate (PEGMMA) nanogels was studied. A novel inverse-emulsion polymerization method was developed, which formed latex nanoparticles on the order of 100-400 nm. The properties of these nanogels were compared to microparticles synthesized via solution polymerization. The new polymerization method allowed the incorporation of PEG surface tethers of lengths 400 Da up to 2000 Da. Surface tethers successfully decreased the ζ-potential of these nanogels from 70 mV to 30 mV in acidic conditions and from −60 mV to 2 mV in basic media. Nanogels swelled from 100 nm in basic media to 800 nm in acidic media due to the protonation of the tertiary amine on DEAEM.

Novel glucose-sensitive systems for the release of insulin from poly(diethylaminoethyl methacrylate) (PDEAEM) micro-particles and nanoparticles decorated with glucose oxidase and catalase enzymes have been developed. The effect of polymer composition and loading conditions on the insulin loading efficiency and release was studied. The optimal conditions for loading insulin into PDEAEM microparticles were found to be at a loading pH of 5.6, particle to insulin mass ratio of 7:1, a concentration of 1.0 mg/mL insulin, and a collapsing pH of approximately 9.5. Microparticles exhibited a responsive (pH) or intelligent (glucose) release of insulin from a stimulus. Microparticles that had a nominal crosslinking ratio of 10% released a third of the insulin payload after a single stimulus, compared to nearly 70% for microparticles with a 3% crosslinking ratio. PDEAEM micro particles of 150 µm diameter showed promise as components of a system of automated, intelligent delivery method for insulin to type I diabetics.

Drug loading and processing conditions in a dry powder inhaler system are critical for performance of the system since it is these forces that must be overcome to properly redisperse respirable particles. In this work, we have investigated the effects of different loading forces for adhering micronized drug onto surfaces on the drug adhesion, detachment, and aerosol performance under controlled conditions. Drug loading onto a standardized surface was performed under three different loading conditions using turbulamixer to actively induce powder-surface interactions. It was seen the drug loading increased with increased processing time. The presence of external press-on force also increased drug loading. Drug detachment studies performed using centrifugation method indicated that adhesion forces were the lowest at lower mixing time and increased with increasing press-on forces. Drug aerosolization performance from the surface was assessed using a prototype DPI and confirmed that external forces during drug loading and coating processing played an important role in drug dispersion. It was seen that the respirability of drug particles correlated with mixing times as well as the press-on forces.

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