UC San Diego

Significant progress over the past decade has transformed oral drug delivery, extending gastric retention time, improving therapeutic efficacy and patient compliance. Cutting-edge innovations leveraging robotic technologies have transformed oral administration, overcoming the limitations of traditional oral delivery and paving the way for a new era of personalized medicine. Nearly 70 years ago, Richard Feynman envisioned ingestible miniaturized medical devices capable of performing surgery within the body. While remarkable advancements have been made since then, Feynman’s dream of “swallow the surgeon” concept remains only partially realized. However, the emergence of microrobotics in active drug delivery is bridging the gap between the pharmaceutical and microrobotic fields, bringing this vision closer to reality. This dissertation presents a time-tunable multi-segment capsule designed to enhance patient adherence to oral medications, particularly in cases of polypharmacy. By simplifying complex medication regimens, this system improves adherence, a crucial factor in chronic disease management and personalized medicine. The capsule enables the programmed release of multiple medications at preselected times, ensuring patient compliance and high therapeutic efficiency. By incorporating micromotors into the capsule, this system enables active drug delivery, improving absorption and bioavailability, optimizing therapeutic outcomes, and seamlessly integrating treatment into patients' daily lives. This advancement marks a major step toward precision drug delivery. Furthermore, incorporating micromotors whether synthetic (e.g., Mg- or Zn-based) or biohybrid (e.g., algae-based) into pharmaceutical carriers represents a groundbreaking approach to active drug delivery, This strategy addresses the limitations of oral drug delivery by leveraging micromotors propulsion for gastrointestinal drug delivery, as demonstrated in vivo using murine and porcine models. Chemical and biological propulsion of micromotors enables immediate disintegration and prolonged gastrointestinal retention, leading to significant dose reduction and enhanced bioavailability. These innovations maximize therapeutic efficacy while minimizing side effects, paving the way for precision therapeutics. Finally, this dissertation explores the future applications of smart robotic capsules, offering a versatile platform. These capsules serve as closed-loop oral devices for continuous monitoring, on-demand drug release, and theranostic applications. By integrating robotic capabilities with multisegment capsule designs, this work envisions a future where there is “plenty of room in a capsule”, a paradigm shifts toward personalized medicine.