Biodegradable PLGA Perfluorocarbon Particles for Ultrasound Imaging
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Solution Overview
Problem
Current contrast agents for ultrasound imaging are unsuitable for cell labeling due to their large size, instability, and limited ability to image smaller blood vessels, leading to challenges in monitoring therapeutic cells in vivo and for drug delivery applications.
Innovation Solution
Development of biodegradable PLGA particles containing a fluorinated organic compound, such as perfluoro crown ether, combined with a metal like gadolinium, which enhances ultrasound and photoacoustic visibility, allowing for stable and quantitative imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If gas-filled microbubbles are used as contrast agents, then ultrasound imaging capability is provided, but the agents have large size (1000-10000 nm) which is unsuitable for cell labeling and cannot image smaller blood vessels
Solution Approach 1:
The patent transforms the physical state of the contrast agent from gas-filled microbubbles (1000-10000 nm) to liquid perfluorocarbon droplets (10-1000 nm) encapsulated in biodegradable polymer shells. This parameter change in size and phase enables the contrast agent to be suitable for cell labeling and imaging of smaller blood vessels while maintaining ultrasound imaging capability.
Solution Approach 2:
The invention creates a composite structure consisting of liquid perfluorocarbon droplets encapsulated within biodegradable polymer shells (such as PLGA). This composite material combines the acoustic properties of perfluorocarbon with the stability and biocompatibility of the polymer shell, resolving the contradiction between imaging capability and appropriate size for cellular applications.
2Reliability
If gas-filled microbubbles are used as contrast agents, then ultrasound imaging is enabled, but the agents have short lifetime (seconds to minutes) and are unstable requiring immediate use after hydration
Solution Approach 1:
The patent employs biodegradable polymer shells (thin films) to encapsulate the liquid perfluorocarbon droplets. These flexible polymer shells provide structural stability, prevent premature dissolution, and enable storage of the contrast agent for extended periods, resolving the instability issue of gas-filled microbubbles while maintaining ultrasound imaging capability.
Solution Approach 2:
The invention uses biodegradable polymer materials that can be safely eliminated from the body after serving their imaging function. The short-lived biodegradable shell provides temporary protection during storage and administration, then naturally degrades in the body, eliminating the need for long-term stability while ensuring safety.
3Reliability
If gas-filled microbubbles are used as contrast agents, then ultrasound imaging is provided, but cell damage may occur as the gas bubbles burst
Solution Approach 1:
The patent converts the harmful bursting behavior of gas-filled microbubbles into a beneficial liquid-based system. By using liquid perfluorocarbon droplets encapsulated in biodegradable shells, the system eliminates the violent bursting that causes cell damage, while the liquid phase provides stable, non-destructive ultrasound imaging capability.
4Reliability
If gas-filled microbubbles are used as contrast agents, then ultrasound imaging is enabled, but the large size encourages prompt clearance by the kidneys limiting useful lifetime in vivo
Solution Approach 1:
The patent changes the size parameter from large gas-filled microbubbles (1000-10000 nm) to small liquid perfluorocarbon droplets (10-1000 nm) with polymer shells. This size reduction below the renal clearance threshold allows the contrast agent to evade kidney filtration, extending in vivo lifetime while maintaining ultrasound imaging capability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The particles provide improved ultrasound and photoacoustic imaging capabilities, enabling effective cell labeling, prolonged visibility, and potential for in vivo targeting and drug delivery, while maintaining biocompatibility and stability under ultrasound exposure.
Implementation Method 1
the ultrasound and photoacoustic visibility of particles greatly improves when the particle contains a fluorinated organic compound in combination with a metal
Implementation Method 2
the ultrasound and photoacoustic visibility of particles greatly improves when the particle contains a fluorinated organic compound in combination with a metal
Data Source
AI summary
The present invention relates to contrast agent enhanced medical ultrasound imaging. In particular, the contrast agents provided are useful for cell imaging and cell therapy, as well as in vivo targeting, drug delivery and perfusion or vascular imaging applications. More specifically, it provides a particle comprising a fluorinated organic compound and a metal. Such particles may be advantageously employed in qualitative or quantitative imaging such as acoustic imaging including photoacoustic and ultrasound imaging, MRI imaging, such as 19F imaging, 1H imaging including T1 and T2 weighted imaging, SPECT, PET, scintigraphy, fluorescence imaging and optical coherence imaging and tomographic applications. This may then be employed in cell labeling, microscopy, histology or for imaging vasculature or perfusion in vivo and in vitro.