ABSTRACT
Oral administration provides a simple and non-invasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics. Here we present an orally dosed liquid auto-injector capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30 min after dosing. This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies. We administered the capsules to swine for delivery of clinically relevant doses of four commonly injected medications, including adalimumab, a GLP-1 analog, recombinant human insulin and epinephrine. These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system.
Subject(s)
Antibodies, Monoclonal , Antineoplastic Agents, Immunological , Administration, Oral , Animals , Biological Availability , Capsules , Immunotherapy , Peptides , SwineABSTRACT
A novel approach to optics integration in ion traps is demonstrated based on a surface electrode ion trap that is microfabricated on top of a dielectric mirror. Additional optical losses due to fabrication are found to be as low as 80 ppm for light at 422 nm. The integrated mirror is used to demonstrate light collection from, and imaging of, a single Sr88(+) ion trapped 169±4 µm above the mirror.
ABSTRACT
We report external cavity second-harmonic generation of light at 544 and 272 nm based on an ytterbium-doped distributed-feedback fiber laser. The nonlinear crystal used to generate light at 544 nm is LiNbO3, and the maximum output of the cavity is 845 mW, corresponding to a conversion efficiency of 55%. In a second frequency-doubling step, using a beta-BaBa2O4 crystal, we generate up to 115 mW of light at 272 nm with a conversion efficiency of 14%.
