(196e) Stable Protein Nanoparticles Produced By Rapid Freezing For Enhanced Delivery | AIChE

(196e) Stable Protein Nanoparticles Produced By Rapid Freezing For Enhanced Delivery

Authors 

Engstrom, J. D. - Presenter, The University of Texas at Austin
Tam, J. - Presenter, The University of Texas at Austin
Lai, E. - Presenter, The University of Texas at Austin
Williams, R. - Presenter, The University of Texas at Austin


Solid protein nanoparticle formulations may be designed to achieve high loadings in parenteral, transdermal and pulmonary delivery. The ability to control the release without the need for daily injections is of paramount importance in the commercialization of the large number of newly discovered therapeutic peptides and proteins. Stable BSA protein nanostructured particles have been encapsulated uniformly into PLA microspheres to achieve high loadings and to reduce the burst release over the first 24 hours. BSA particles have been designed to achieve optimal aerodynamic diameters for pulmonary delivery. Protein nanocrystals with unusually high stability were formed with novel spray freezing and thin film freezing processes, by minimizing the time of exposure of protein to air-water and ice-water interfaces. The morphology of the protein particles is described as a function of the nucleation and growth rates, which depend upon the cooling rate. Enzyme activities were determined for lactate dehydrogenase (LDH) particles produced by lyophilization, and three fast freezing processes, spray freeze-drying (SFD), spray freezing into liquid (SFL) nitrogen and thin film freezing. The SFL and thin film freezing processes produced high enzyme activities, comparable to lyophilization, despite particle diameters that were an order of magnitude smaller. The formation of stable solid protein particles, with diameters smaller than one micron, offers new opportunities in a variety of drug delivery applications.