Aim: We developed a platform to painlessly deliver by mouth drugs that cannot be administered orally. This ingestible, capsule-like device deploys inside the small intestine and injects into its wall a biotherapeutic payload sealed inside a dissolvable microneedle.
Results: We tested the delivery and examined the pharmacokinetics of several biopharmaceuticals, including recombinant human insulin, human immunoglobulin G, octreotide and teriparatide in anesthetized and conscious pigs and dogs. The bioavailability of these compounds delivered by the capsules was similar to that after subcutaneous delivery. For instance, the mean peak serum concentration of insulin after capsule delivery in 8 anesthetized pigs was 517 ± 109 pmol/l, versus 342 ± 50 pmol/l after subcutaneous injection in 9 other, sham-operated pigs. In vivo safety studies were conducted in 23 conscious beagles, which received between 2 and 18 capsules. All devices transited painlessly through the GI tract and were excreted within 96 h. The mean gastric residence time (GRT) of the capsules was 93 min, and subsequent intestinal deployment time (IDT) was 28 minutes. A pilot study in 10 fasting and 10 postprandial human volunteers examined the tolerability and safety of the capsule devoid of microneedle and payload. The mean GRT of the capsule was 217 ± 36 min in the postprandial and 100 ± 79 min in the fasting state, while the IDT were closely similar (100 ± 40 vs. 97 ± 30 min) in both groups. No subject perceived the device transit, deployment or excretion.
Conclusions: The studies completed thus far in anesthetized or conscious animals have confirmed that this ingestible device can deliver drugs in sufficient amounts and rate to obtain therapeutic blood concentrations. Its oral administration was well tolerated by the human subjects. First-in-man studies are being planned to test the ability of this ingestible device to deliver pharmaceuticals in healthy human volunteers and patients.
R. Ruffy: Employee; Self; RANI Therapeutics. M. Hashim: Board Member; Self; Rani Therapeutics. Employee; Self; InCube Labs LLC. A. Dhalla: Employee; Self; Rani Therapeutics, LLC. R. Korupolu: None. P. Karamchedu: Employee; Self; Incube labaoratories, Rani Therapeutics. B. Syed: None. R. Abdul Wahab: Employee; Self; Rani Therapeutics. S. Beraki: Employee; Self; InCube Laboratories, RANI Therapeutics. A. Yamaguchi: Employee; Self; Rani Therapeutics. L. Fusaro: None. A. Garapaty: None. A. Dasari: None. L. Fung: Employee; Self; Rani Therapeutics. Z.T. Al-Shamsie: Employee; Spouse/Partner; Google. Employee; Self; Rani Therapeutics, InCube Labs LLC. A. Toledo: Employee; Self; InCube Labs LLC, Rani Therapeutics. V. Salgotra: Employee; Self; Incubelabs, Rani Therapeutics. S. Sharma: None. E. Liang: None. D. Gratta: Employee; Self; InCube Labs, Rani Theraputics. M. Imran: Other Relationship; Self; InCube Labs, InCube Ventures, Rani Therapeutics.