Alginate Microspheres Containing Temperature Sensitive Liposomes (TSL) for MR-Guided Embolization and Triggered Release of Doxorubicin.

Abstract

OBJECTIVE:

The objective of this study was to develop and characterize alginate microspheres suitable for embolization with on-demand triggered doxorubicin (DOX) release and whereby the microspheres as well as the drug releasing process can be visualized in vivo using MRI.

METHODS AND FINDINGS:

For this purpose, barium crosslinked alginate microspheres were loaded with temperature sensitive liposomes (TSL/TSL-Ba-ms), which release their payload upon mild hyperthermia. These TSL contained DOX and [Gd(HPDO3A)(H2O)], a T1 MRI contrast agent, for real time visualization of the release. Empty alginate microspheres crosslinked with holmium ions (T2* MRI contrast agent, Ho-ms) were mixed with TSL-Ba-ms to allow microsphere visualization. TSL-Ba-ms and Ho-ms were prepared with a homemade spray device and sized by sieving. Encapsulation of TSL in barium crosslinked microspheres changed the triggered release properties only slightly: 95% of the loaded DOX was released from free TSL vs. 86% release for TSL-Ba-ms within 30 seconds in 50% FBS at 42°C. TSL-Ba-ms (76 ± 41 μm) and Ho-ms (64 ± 29 μm) had a comparable size, which most likely will result in a similar in vivo tissue distribution after an i.v. co-injection and therefore Ho-ms can be used as tracer for the TSL-Ba-ms. MR imaging of a TSL-Ba-ms and Ho-ms mixture (ratio 95:5) before and after hyperthermia allowed in vitro and in vivo visualization of microsphere deposition (T2*-weighted images) as well as temperature-triggered release (T1-weighted images). The [Gd(HPDO3A)(H2O)] release and clusters of microspheres containing holmium ions were visualized in a VX2 tumor model in a rabbit using MRI.

CONCLUSIONS:

In conclusion, these TSL-Ba-ms and Ho-ms are promising systems for real-time, MR-guided embolization and triggered release of drugs in vivo.

• Authors: Merel van Elk, Burcin Ozbakir, Angelique D Barten-Rijbroek, Gert Storm, Frank Nijsen, Wim E Hennink, Tina Vermonden, Roel Deckers
• Journal: PloS one (PLoS One) Vol. 10 Issue 11 Pg. e0141626 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26561370 (Publication Type: Journal Article)

Chemical References

• Alginates
• Antibiotics, Antineoplastic
• Hexuronic Acids
• Liposomes
• Doxorubicin
• Glucuronic Acid

Topics

• Alginates (chemistry)
• Animals
• Antibiotics, Antineoplastic (administration & dosage)
• Doxorubicin (administration & dosage)
• Embolization, Therapeutic
• Glucuronic Acid (chemistry)
• Hexuronic Acids (chemistry)
• Liposomes
• Magnetic Resonance Imaging
• Microspheres
• Rabbits
• Temperature