9.3 Drug delivery systems and smart prosthetics

Drug delivery systems and smart prosthetics are revolutionizing healthcare. These technologies enable precise medication administration and restore lost functionality. From controlled-release pills to neural-controlled limbs, MEMS and NEMS are transforming patient care and quality of life.

Microdevices like implantable reservoirs and microneedles offer targeted drug delivery with minimal invasiveness. Smart prosthetics incorporate sensors and neural interfaces, allowing intuitive control and sensory feedback. These advancements showcase the potential of micro and nanotechnology in biomedical applications.

Drug Delivery Methods

Controlled Release and Targeted Delivery Systems

• Controlled release systems enable precise dosage and timing of drug administration over an extended period
  • Reduces frequency of dosing and maintains therapeutic levels (extended-release tablets)
  • Minimizes side effects by avoiding high peak concentrations
• Targeted drug delivery directs medications to specific tissues, cells, or receptors
  • Enhances therapeutic efficacy and reduces off-target effects (antibody-drug conjugates targeting cancer cells)
  • Utilizes targeting moieties such as antibodies, peptides, or aptamers to bind specific receptors or antigens
• Transdermal patches deliver drugs through the skin, allowing for sustained release and bypassing first-pass metabolism
  • Commonly used for nicotine replacement therapy, pain management (fentanyl patches), and hormone replacement (estradiol patches)
  • Enables convenient, non-invasive administration and improves patient compliance

Advanced Oral and Nanoparticle-Based Delivery Systems

• Smart pills contain embedded sensors or microchips to monitor drug release, adherence, and physiological parameters
  • Ingestible sensors can transmit data to external devices for real-time monitoring (Proteus Digital Health's ingestible sensor)
  • Enables personalized dosing, improved adherence, and early detection of adverse events
• Nanoparticle drug carriers, such as liposomes, polymeric nanoparticles, and micelles, encapsulate and deliver drugs to target sites
  • Enhances drug solubility, stability, and bioavailability
  • Enables passive targeting through enhanced permeability and retention effect in tumors (Doxil, PEGylated liposomal doxorubicin)
  • Allows for active targeting by surface functionalization with targeting ligands

Microdevices for Drug Delivery

Implantable Microreservoirs and Microneedles

• Microreservoirs are miniaturized drug storage and release devices implanted in the body
  • Consist of arrays of reservoirs etched into silicon or polymer substrates
  • Reservoirs are filled with drugs and sealed with stimuli-responsive membranes (pH, temperature, or electric field-sensitive)
  • Enables pulsatile or on-demand drug release triggered by external stimuli or physiological signals
• Microneedles are micron-scale needles that painlessly penetrate the skin to deliver drugs or extract biological fluids
  • Can be solid, coated, dissolving, or hollow for drug delivery or sensing applications
  • Enhances transdermal drug delivery by overcoming the stratum corneum barrier (influenza vaccine-coated microneedles)
  • Minimally invasive and reduces risk of infection compared to hypodermic needles

Bioresorbable Materials for Drug Delivery

• Bioresorbable materials, such as polymers (PLGA, PLA) and ceramics (calcium phosphates), degrade in the body over time
  • Eliminates the need for surgical removal of implanted drug delivery devices
  • Degradation rate can be tuned to match the desired drug release profile
  • Byproducts are safely metabolized and excreted by the body
• Bioresorbable drug delivery systems include implants, microparticles, and nanofibers
  • Provide localized and sustained drug release for applications such as bone regeneration, wound healing, and cancer therapy (Gliadel wafers for glioblastoma treatment)

Smart Prosthetics

Advanced Prosthetic Limbs and Neural Interfaces

• Prosthetic limbs have evolved to incorporate sensors, actuators, and control systems for improved functionality and user experience
  • Myoelectric prostheses use electromyographic signals from residual muscles to control the prosthetic limb (i-Limb hand)
  • Osseointegrated prostheses are directly anchored to the bone, providing enhanced stability and sensory feedback
• Neural-machine interfaces enable bidirectional communication between the nervous system and prosthetic devices
  • Invasive interfaces, such as intracortical microelectrode arrays, record neural signals directly from the brain (BrainGate)
  • Non-invasive interfaces, such as electroencephalography (EEG) and electromyography (EMG), record neural signals from the scalp or skin surface
  • Sensory feedback can be provided through electrical stimulation of peripheral nerves or brain regions, restoring a sense of touch and proprioception
• Advanced control algorithms and machine learning techniques enable intuitive and adaptive control of prosthetic limbs
  • Pattern recognition algorithms classify EMG signals to identify intended movements (COAPT system)
  • Reinforcement learning allows the prosthesis to adapt to the user's preferences and environment over time