A Factorial Approach for Optimizing the Design Parameters of a Tissue Attachment Mechanism for Drug Delivery.

Biological macromolecule drugs or biologics are not suited for commonly preferred oral delivery due to their intrinsic instability and physical, chemical, or immunological barriers to the gastrointestinal tract. Ingestible capsule robots (ICR) have become a versatile platform, including use for drug delivery applications for various gastrointestinal pathologies with future potential for systemic drug delivery. In this work, a tissue attachment mechanism (TAM) for a drug delivery ICR is introduced that can facilitate a non-invasive systemic delivery of unaltered biologics via direct injection through the insensate layers of the small intestine. The main prerequisite for achieving systemic drug delivery via this device is to have a strong tissue attachment of the TAM. This study aimed to optimize the attachment success rate for drug delivery and characterize attachment duration in vivo. A fractional factorial approach was used in vivo to identify and optimize factors that most influence attachment of the TAM to maximize attachment rate. Multiple in vivo optimization levels were performed using the small intestine of anesthetized pigs, and an attachment success rate of 92% was achieved. Optimal TAMs were surgically placed in vivo to determine the duration of attachment following anesthetization and surgery recovery. The average in vivo attachment duration was 32.2±9.4 hours. This work establishes a device for consistent and reliable attachment duration, making the TAM a suitable candidate for a 24-hour systemic drug delivery platform.

A Novel Capsule-Delivered Enteric Drug-Injection Device for Delivery of Systemic Biologics: A Pilot Study in a Porcine Model.

Innovative swallowable capsule technologies such as drug-loaded, dissolvable microneedles, mucoadhesive patches, and various microdevices present unique drug-carrying capabilities to overcome challenges regarding oral delivery of biologics. Here, we report a swallowable capsule for intestinal drug delivery (SCIDD) with the potential of directly injecting biological therapeutics into the insensate small intestine wall. The design, optimization, and validation of the SCIDD's primary subsystems were performed both ex-vivo and in-vivo. The assembled capsule was further tested in vivo to validate the actuation sequence and showed a 70% (n = 17) success rate in an animal model. Additionally, a drug delivery study indicated systemic uptake of adalimumab via SCIDD compared with luminal delivery in the small intestine. The pilot study presented here establishes that the novel platform could be used to orally deliver systemic biologics.