Towards soft robotic devices for site-specific drug delivery

Abstract

Considerable research efforts have recently been dedicated to the establishment of various drug delivery systems (DDS) that are mechanical/physical, chemical and biological/molecular DDS. In this paper, we report on the recent advances in site-specific drug delivery (site-specific, controlled, targeted or smart drug delivery are terms used interchangeably in the literature, to mean to transport a drug or a therapeutic agent to a desired location within the body and release it as desired with negligibly small toxicity and side effect compared to classical drug administration means such as peroral, parenteral, transmucosal, topical and inhalation) based on mechanical/physical systems consisting of implantable and robotic drug delivery systems. While we specifically focus on the robotic or autonomous DDS, which can be reprogrammable and provide multiple doses of a drug at a required time and rate, we briefly cover the implanted DDS, which are well-developed relative to the robotic DDS, to highlight the design and performance requirements, and investigate issues associated with the robotic DDS. Critical research issues associated with both DDSs are presented to describe the research challenges ahead of us in order to establish soft robotic devices for clinical and biomedical applications.

Keywords:

• capsule endoscope
• gastrointestinal tract
• magnetic drug carriers
• robotic capsules
• robotic drug delivery systems
• site-specific drug delivery
• soft robotics

Acknowledgements

The author wishes to gratefully acknowledge the help of Dr. Madeleine Strong Cincotta in the final language editing of this paper, and help of Dr Rahim Mutlu, Dr Hao Zhou and Mr Fredy Munoz in preparing Figures 3–6. The author acknowledges that some of the relevant studies in the published literature may not have been included in this review.

Financial & competing interests disclosure

This work is partly supported by the ARC Centre of Excellence for Electromaterials (ACES) (Grant No. CE140100012) received by G Alici. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Site-specific drug delivery refers to physically carrying or transporting a drug to a specific location within the body, and discharging or releasing an appropriate (optimal) dose and rate of it when desired.

• Site-specific DDS are classified into mechanical/physical, chemical and biological/molecular DDS.

• Mechanical/physical DDS are further divided into implantable and robotic/autonomous DDS. We focus on the latter, which is still in its infancy and raises significant research questions that must be answered before it can meet the strict application, technical and regulation requirements.

• Implantable DDS can be incorporated into the container-based robotic DDS as their drug-release mechanism.

• Magnetic actuation acts remotely, negating the need for an on-board power source for implantable micropump DDS. This significantly decreases the size of the micropumps.

• If an implantable DDS requires on-board power, there is a need for high energy density batteries such as Li–ion batteries or the power must be induced wirelessly using a magnetic induction technique, which is complex to implement and operate. This applies to container-based robotic DDS, too.

• A container-based robotic DDS needs a minimum size as large as a vitamin pill, like a typical endoscopic capsule.

• A container-based robotic DDS must have actuation, localization, anchoring and drug-release mechanisms intelligently hidden within its compact size.

• The progress in soft robotic devices for medical applications depends on the progress in soft, biocompatible and printable materials amenable to remote stimuli such as magnetic field or heat field, not requiring any on-board energy source.

• With current technology, it is not possible to have an autonomous robotic system with an on-board energy source, making magnetic actuation a strong candidate to articulate the robotic system.

• An external magnetic system remotely navigates a target robotic device in the body, assuming that the anchoring and drug-release mechanisms can be activated using an on-board power source, which will intermittently be used during the anchoring and drug-release times only.

• Swarm-based DDS in the form of bacterial microsystems are inspired from the flagellar bacteria, usually requiring a remotely applied magnetic field.

• Swarm-based DDS responsive to a magnetic field are the most effective ones to guide the device to a desired site.

• The research challenges for the container-based robotic DDS are the same as the actively operated endoscopic capsules.

Notes