Abstract
| Original language | English |
|---|---|
| Article number | e141626 |
| Pages (from-to) | e0141626- |
| Journal | PLoS ONE |
| Volume | 10 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2015 |
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Keywords
- METIS-315213
- IR-99650
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Alginate microspheres containing temperature sensitive liposomes (TSL) for MR-guided embolization and triggered release of doxorubicin. / van Elk, M.; Ozbakir, B.; Barten-Rijbroek, A.D.; Storm, Gerrit; Nijsen, F.; Hennink, W.E.; Vermonden, T.; Deckers, R.
In: PLoS ONE, Vol. 10, No. 11, e141626, 2015, p. e0141626-.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Alginate microspheres containing temperature sensitive liposomes (TSL) for MR-guided embolization and triggered release of doxorubicin
AU - van Elk, M.
AU - Ozbakir, B.
AU - Barten-Rijbroek, A.D.
AU - Storm, Gerrit
AU - Nijsen, F.
AU - Hennink, W.E.
AU - Vermonden, T.
AU - Deckers, R.
N1 - Open access
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - METIS-315213
KW - IR-99650
U2 - 10.1371/journal.pone.0141626
DO - 10.1371/journal.pone.0141626
M3 - Article
VL - 10
SP - e0141626-
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 11
M1 - e141626
ER -