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Freeze-Dried Therapeutic Microbubbles: Stability and Gas Exchange
Radwa H Abou-Saleh1,2, Aileen Delaney1, Nicola Ingram3
1Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, U.K.
ACS Applied Bio Materials
|January 12, 2022
Summary
Freeze-drying enables long-term storage of therapeutic microbubbles (thMBs) with attached drug payloads. These reconstituted thMBs maintain structural integrity, drug loading, and echogenicity for potential clinical use.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Nanotechnology
Background:
- Microbubbles (MBs) are vital ultrasound contrast agents and drug delivery vehicles.
- Limited MB stability restricts their clinical application and therapeutic potential.
- Therapeutic microbubbles (thMBs) with drug payloads face significant stability and production challenges.
Purpose of the Study:
- To develop a method for freeze-drying and reconstituting therapeutic microbubbles (thMBs) with liposomal drug payloads.
- To assess the stability, structural integrity, and drug retention of freeze-dried thMBs.
- To evaluate the in vivo performance and gas core exchange capabilities of reconstituted thMBs.
Main Methods:
- Microfluidic production of lipid-coated MBs with attached liposomes containing calcein or gemcitabine.
- Freeze-drying and reconstitution of drug-loaded thMBs.
- Assessment of structural integrity, drug loading, in vivo echogenicity, and gas core exchange.
Main Results:
- Drug-loaded thMBs were successfully freeze-dried and stored for over 6 months.
- Reconstituted thMBs retained structural integrity and drug loading.
- In vivo echogenicity was maintained post-freeze-drying, with demonstrated gas core exchange capabilities.
Conclusions:
- Freeze-drying offers a viable method for long-term storage and transport of thMBs.
- This technique facilitates off-site production and point-of-care reformulation of thMBs.
- The developed method supports the clinical translation of therapeutic microbubbles for enhanced drug delivery and combination therapies.
