Microbubbles containing lysolipid enhance ultrasound‐mediated blood–brain barrier breakdown in vivo
Ultrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood–brain barrier (BBB) permeability to therapeutics. To reduce off‐target effects, it is desirable to minimize the ultrasound pressures required. It has been shown that a new formulation of MBs containing lysoli...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2020
|
| _version_ | 1797084923231731712 |
|---|---|
| author | Vince, O Peeters, S Johanssen, VA Gray, M Smart, S Sibson, NR Stride, E |
| author_facet | Vince, O Peeters, S Johanssen, VA Gray, M Smart, S Sibson, NR Stride, E |
| author_sort | Vince, O |
| collection | OXFORD |
| description | Ultrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood–brain barrier (BBB) permeability to therapeutics. To reduce off‐target effects, it is desirable to minimize the ultrasound pressures required. It has been shown that a new formulation of MBs containing lysolipids (Lyso‐MBs) can increase the cellular uptake of a model drug in vitro. The aim of this study is to investigate whether Lyso‐MBs can also enhance BBB permeability in vivo. Female BALB/c mice are injected with either Lyso‐MBs or control MBs and gadolinium‐DTPA (Gd‐DTPA) and exposed to ultrasound (500 kHz, 1 Hz pulse repetition frequency, 1 ms pulse length, peak‐negative pressures 160–480 kPa) for 2 min. BBB permeabilization is measured via magnetic resonance imaging (7.0 T) of Gd‐DTPA extravasation and subsequent histological examination of brain tissue to assess serum immunoglobulin G (IgG) extravasation (n = 8 per group). An approximately twofold enhancement in BBB permeability is produced by the Lyso‐MBs at the highest ultrasound pressure compared with the control. These findings indicate that modifying the composition of phospholipid‐shelled MBs has the potential to improve the efficiency of BBB opening, without increasing the ultrasound pressure amplitude required. This is particularly relevant for delivery of therapeutics deep within the brain.
|
| first_indexed | 2024-03-07T02:01:56Z |
| format | Journal article |
| id | oxford-uuid:9dab75e9-e735-4d19-bb55-21d3ee8d3ac5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:01:56Z |
| publishDate | 2020 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:9dab75e9-e735-4d19-bb55-21d3ee8d3ac52022-03-27T00:44:46ZMicrobubbles containing lysolipid enhance ultrasound‐mediated blood–brain barrier breakdown in vivoJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9dab75e9-e735-4d19-bb55-21d3ee8d3ac5EnglishSymplectic ElementsWiley2020Vince, OPeeters, SJohanssen, VAGray, MSmart, SSibson, NRStride, EUltrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood–brain barrier (BBB) permeability to therapeutics. To reduce off‐target effects, it is desirable to minimize the ultrasound pressures required. It has been shown that a new formulation of MBs containing lysolipids (Lyso‐MBs) can increase the cellular uptake of a model drug in vitro. The aim of this study is to investigate whether Lyso‐MBs can also enhance BBB permeability in vivo. Female BALB/c mice are injected with either Lyso‐MBs or control MBs and gadolinium‐DTPA (Gd‐DTPA) and exposed to ultrasound (500 kHz, 1 Hz pulse repetition frequency, 1 ms pulse length, peak‐negative pressures 160–480 kPa) for 2 min. BBB permeabilization is measured via magnetic resonance imaging (7.0 T) of Gd‐DTPA extravasation and subsequent histological examination of brain tissue to assess serum immunoglobulin G (IgG) extravasation (n = 8 per group). An approximately twofold enhancement in BBB permeability is produced by the Lyso‐MBs at the highest ultrasound pressure compared with the control. These findings indicate that modifying the composition of phospholipid‐shelled MBs has the potential to improve the efficiency of BBB opening, without increasing the ultrasound pressure amplitude required. This is particularly relevant for delivery of therapeutics deep within the brain. |
| spellingShingle | Vince, O Peeters, S Johanssen, VA Gray, M Smart, S Sibson, NR Stride, E Microbubbles containing lysolipid enhance ultrasound‐mediated blood–brain barrier breakdown in vivo |
| title | Microbubbles containing lysolipid enhance ultrasound‐mediated blood–brain barrier breakdown in vivo |
| title_full | Microbubbles containing lysolipid enhance ultrasound‐mediated blood–brain barrier breakdown in vivo |
| title_fullStr | Microbubbles containing lysolipid enhance ultrasound‐mediated blood–brain barrier breakdown in vivo |
| title_full_unstemmed | Microbubbles containing lysolipid enhance ultrasound‐mediated blood–brain barrier breakdown in vivo |
| title_short | Microbubbles containing lysolipid enhance ultrasound‐mediated blood–brain barrier breakdown in vivo |
| title_sort | microbubbles containing lysolipid enhance ultrasound mediated blood brain barrier breakdown in vivo |
| work_keys_str_mv | AT vinceo microbubblescontaininglysolipidenhanceultrasoundmediatedbloodbrainbarrierbreakdowninvivo AT peeterss microbubblescontaininglysolipidenhanceultrasoundmediatedbloodbrainbarrierbreakdowninvivo AT johanssenva microbubblescontaininglysolipidenhanceultrasoundmediatedbloodbrainbarrierbreakdowninvivo AT graym microbubblescontaininglysolipidenhanceultrasoundmediatedbloodbrainbarrierbreakdowninvivo AT smarts microbubblescontaininglysolipidenhanceultrasoundmediatedbloodbrainbarrierbreakdowninvivo AT sibsonnr microbubblescontaininglysolipidenhanceultrasoundmediatedbloodbrainbarrierbreakdowninvivo AT stridee microbubblescontaininglysolipidenhanceultrasoundmediatedbloodbrainbarrierbreakdowninvivo |