Pulsatile localized drug releases from microdevices delivered by a single injection

Applications

A proprietary polymer-based microdevice designed for local delivery of therapeutics (including STING-agonists) at multiple, delayed-release time points over a 0-12 month period following a single injection

Problem Addressed

One of the promising ways to improve the responses of cancer immunotherapies is the intratumoral co-administration of STING-agonists to stimulate an innate immune response. The current dose regimen requires multiple injections of STING-agonists over the course of months, which demands frequent hospital visits and results in low compliance rates. Additionally, with every injection comes the increasing risks of acquiring hospital infections and stimulating metastasis, as shots are administered at local tumor sites and can perturb vascular networks and the tumor microenvironment. Our technology eliminates these problems by administering a single dose of programmable polymer-based microparticles that can release STING-agonists (or other therapeutic agents) at the site of injection in short, timed-release pulses over the course of months with essentially no leakage between pulses.

Technology

Microdevices: 

  • Made with polydimethylsiloxane (PDMS) micromolding, 3D printing or stereolithography using FDA-approved biodegradable polylactic-co-glycolic acid (PLGA) for low cost mass production
  • Adjustable wall thicknesses for the microparticles with ratios of the manufacturing polymers adjusted to control the timing of pulsatile drug releases
  • The hollow core of the microdevice is filled with a drug using an ink jet piezoelectric nozzle and then tightly sealed with an aligned polymeric cap to prevent leakage
  • Devices allow stable encapsulation of different types of nucleic acid and small molecule STING-agonists, or alternatively, other biologic or chemical agents for sustained release delivery

Administration of multiple doses in single injection:

  • Mixed populations of two or more microdevices made with different polymeric compositions are injected at a local tissue site (optimized for drug release kinetics from days to months later)
  • Devices are delivered using standard 23 gauge needles and remain localized at injection sites
  • Single injection STING-agonist delivery triggers local and systemic antitumor immune responses and inhibits tumor growth as effectively as multiple doses of soluble STING agonist
  • Platform can be used for delivery of oncology, vaccine, pain and other classes of therapeutics

Advantages

  • Higher compliance – Eliminates multiple hospital visits due to single injection and lowers costs
  • Reduces risk of metastasis – Single injection reduces tumor microenvironment perturbations
  • Programmable release – Can easily control the time of delayed drug release on the order of days, weeks or months by changing the lactide:glycolide ratio
  • Versatile Platform – Encapsulates and releases any type of multi-dose therapeutic payload
  • Low toxicity – Microdevices can be manufactured from multiple FDA-approved and commercially available biocompatible and biodegradable polymers