Increasing the stiffness of these scientific study particles by increasing hydrogel crosslink density can reduce the elimination half-life 30-fold and change the accumulation of these particles from the spleen to the lungs and liver. These two studies highlight the importance that flexible control of particle size, shape, and chemistry affords drug delivery vehicles. Additionally, the PRINT

manufacturing process has been demonstrated at Lapatinib chemical structure scales relevant Inhibitors,research,lifescience,medical to support preclinical and clinical studies. Liquidia Technologies has initiated a Phase I clinical study of a PRINT vaccine candidate, demonstrating the production of GMP pharmaceutical materials using this novel nanofabrication process, at a scale relevant to clinical development [16]. The outcome of implementing this particle engineering approach for dry powder fabrication is improved aerosol Inhibitors,research,lifescience,medical performance applicable to respiratory drug delivery, demonstrated by incorporation of a variety of pharmaceutically relevant compounds. In vitro results demonstrate that PRINT particle aerosols possess high respirable dose, high fine particle fraction, and tunable particle aerodynamic diameter. In vivo canine deposition studies demonstrate the ability to influence dry powder delivery as a function of particle geometry. These results suggest that this tunable particle engineering approach is a versatile platform for Inhibitors,research,lifescience,medical enabling next-generation Inhibitors,research,lifescience,medical respiratory drug

delivery. We also highlight some of the utility of PRINT for the production of particles for small molecule, protein, and oligonucleotide drug delivery, which demonstrates that PRINT is a versatile formulation approach

and should find applicability in oral, parenteral, and topical dosage forms for multiple disease indications. 2. Methods 2.1. Fabrication of Particles for Drug Delivery Using PRINT Technology PRINT is an adaptation of micro- and nanomolding technologies, rooted in the microelectronics industry, that is used to fabricate monodisperse particles of controlled sizes and shapes using roll-to-roll manufacturing processes. It allows for the Inhibitors,research,lifescience,medical fabrication of monodisperse particles with Dacomitinib precise control over size, shape, composition, and surface functionalization. Unlike many other particle fabrication techniques, the PRINT method is versatile and gentle enough to be compatible with the multitude of next-generation therapeutic and diagnostic agents, including small molecules, protein biologics, siRNA, and bioabsorbable and hydrophilic polymer matrix materials with embedded pharmaceutical cargo. An overview of the PRINT process is outlined in Figure 1. As mentioned previously, the particles produced using the PRINT process are templated using polymeric micromolds. The molds themselves arise from replication of a silicon master template (Figure 1(a)), which is fabricated using advanced lithographic techniques.