In this work, we highlight the ability of PRINT to fabricate particles of neat small molecule drugs. Figures 2(d)–2(f) show particles composed

of 100% itraconazole, prepared by molding an amorphous itraconazole glass. Particles composed of zanamivir were also fabricated (Figure 2(g)), and both itraconazole and zanamivir particles showed good aerosol delivery performance in vitro (Figures ​(Figures33 and ​and44). PRINT particles can be prepared from protein and oligonucleotide therapeutic agents as well. Kelly and DeSimone demonstrated the capability to use PRINT Inhibitors,research,lifescience,medical technology to fabricate monodisperse particles of albumin and insulin Inhibitors,research,lifescience,medical without causing agglomeration of the protein [12]. In this work, we demonstrate molding of DNase, a therapeutic protein for cystic fibrosis (marketed as Pulmozyme). Figure 2(h) shows 1.5μm torus particles composed of DNase. Size exclusion chromatography of PRINT-DNase microparticles shows minimal agglomeration of the protein,

and in vitro bioassay measurements demonstrate equivalent enzyme activity to naïve DNase. Oligonucleotide molecules such as siRNA therapeutics were also successfully molded Inhibitors,research,lifescience,medical as particles (Figure 2(i)) with retention of chemical structure. Taken together, these data demonstrate that PRINT particles can be formed of biological materials without aggregating/denaturing the molecule or changing its functionality. Micromolded particles produce high-performance aerosols that possess tunable aerodynamic diameters and narrow aerodynamic size distributions. This control over aerosol characteristics was demonstrated across a wide range of aerodynamic diameters within the respirable range (Figure 3(a)) and through Inhibitors,research,lifescience,medical differential in vivo lung deposition based on learn more particle Inhibitors,research,lifescience,medical size (Figure 4(c)). In addition, PRINT aerosols achieve an increased respirable dose and decreased MMAD, including

the dose fraction below 1.6μm, compared to aerosols generated by traditional micronization processes (Figures 3(b) and 4(a)). These attributes are expected to translate into more efficient respiratory drug delivery for a wide isothipendyl range of therapeutics that are intended to deposit in the lung periphery. Importantly, the aerosolization of PRINT particle dry powders does not require the use of bulking excipients, such as lactose, for particle dispersion, as is often the case for dry powder products. Elimination of bulking agents potentially simplifies the chemistry, manufacturing, and control processes required to develop dry powder products, as well as mitigating the potential for excipient-induced user side effects. The micromolding particle fabrication approach presented here also holds the potential to engineer dry powder aerosols optimized for specific disease targets.