Ultrasound-triggered drug release from liposomes using nanoscale cavitation nuclei
<p>Side effects of current chemotherapeutics limit their use in cancer therapy. Although many current drugs are highly toxic and potent, the effects they have on non-cancerous tissue are unbearable for patients. Targeting these drugs may provide a means to restrict their toxic effects to only...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
2014
|
| Subjects: |
| _version_ | 1817933138349785088 |
|---|---|
| author | Graham, S Susan M Graham |
| author2 | Coussios, C |
| author_facet | Coussios, C Graham, S Susan M Graham |
| author_sort | Graham, S |
| collection | OXFORD |
| description | <p>Side effects of current chemotherapeutics limit their use in cancer therapy. Although many current drugs are highly toxic and potent, the effects they have on non-cancerous tissue are unbearable for patients. Targeting these drugs may provide a means to restrict their toxic effects to only cancer tissue while leaving healthy tissue unaffected. This approach requires that the drug is only available in cancer tissue, which has been achieved here by encapsulating drugs into liposomal nano-capsules which are capable of passively accumulating in cancerous tissue via the enhanced permeability and retention effect (EPR). In addition to localisation, a threshold dose must be achieved to deliver the desired toxic effect to the target tumour tissue. Previous strategies have relied on passive 'leaching' of the drug from liposomes, however this 'leaching' does not necessarily achieve the threshold dose required. In the present work, a new generation of liposomes has been developed whereby release is solely achieved in the presence of ultrasound triggered cavitation.</p> <p>Instigation of such cavitation events would normally require the target tissue be exposed to high and possibly damaging ultrasound pressures. To remove the need for these high pressures, cavitation nuclei have been developed to lower the cavitation threshold of surrounding media. To allow for improved co-localisation and treatment deeper into cancer tissue, cavitation nuclei were developed to be in the nanoscale size range. Two types of novel cavitation nuclei were produced, a rough surfaced carbon nanoparticle (CNP, ~180 nm) and smooth shaped polymeric nano-cup particle (NC, ~150, 470, or 770 nm). Both types of particle are solid nanoparticles with gas entrapped on their surface which was capable of cavitating in response to ultrasound without greatly affecting the particle itself. These particles are classified as cavicatalytic nanoparticles due to their ability to reduce the cavitation threshold of their surrounding media without being destroyed themselves. Finally, an entirely nanoscale release system was developed and tested <em>in vitro</em> and <em>in vivo</em>. The drug carrier (the liposome) and effector agent (the cavicatalytic nanoparticle) were used to demonstrate ultrasound triggered drug release, specifically in response to the generation of cavitation events. These cavitation events could be non-invasively monitored and characterised, adding to the potential clinical utility of the technologies developed and described here.</p> |
| first_indexed | 2024-03-06T22:08:39Z |
| format | Thesis |
| id | oxford-uuid:510ab12d-74c9-4c07-a621-4dc388b14f7a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:49:02Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:510ab12d-74c9-4c07-a621-4dc388b14f7a2024-12-08T12:13:46ZUltrasound-triggered drug release from liposomes using nanoscale cavitation nucleiThesishttp://purl.org/coar/resource_type/c_db06uuid:510ab12d-74c9-4c07-a621-4dc388b14f7aMedical SciencesNano-biotechnologyOncologyHigh Intensity Focussed Ultrasound (HIFU)Biomedical engineeringNanomaterialsEngineering & allied sciencesNanostructuresLife SciencesEnglishOxford University Research Archive - Valet2014Graham, SSusan M GrahamCoussios, CCarlisle, R<p>Side effects of current chemotherapeutics limit their use in cancer therapy. Although many current drugs are highly toxic and potent, the effects they have on non-cancerous tissue are unbearable for patients. Targeting these drugs may provide a means to restrict their toxic effects to only cancer tissue while leaving healthy tissue unaffected. This approach requires that the drug is only available in cancer tissue, which has been achieved here by encapsulating drugs into liposomal nano-capsules which are capable of passively accumulating in cancerous tissue via the enhanced permeability and retention effect (EPR). In addition to localisation, a threshold dose must be achieved to deliver the desired toxic effect to the target tumour tissue. Previous strategies have relied on passive 'leaching' of the drug from liposomes, however this 'leaching' does not necessarily achieve the threshold dose required. In the present work, a new generation of liposomes has been developed whereby release is solely achieved in the presence of ultrasound triggered cavitation.</p> <p>Instigation of such cavitation events would normally require the target tissue be exposed to high and possibly damaging ultrasound pressures. To remove the need for these high pressures, cavitation nuclei have been developed to lower the cavitation threshold of surrounding media. To allow for improved co-localisation and treatment deeper into cancer tissue, cavitation nuclei were developed to be in the nanoscale size range. Two types of novel cavitation nuclei were produced, a rough surfaced carbon nanoparticle (CNP, ~180 nm) and smooth shaped polymeric nano-cup particle (NC, ~150, 470, or 770 nm). Both types of particle are solid nanoparticles with gas entrapped on their surface which was capable of cavitating in response to ultrasound without greatly affecting the particle itself. These particles are classified as cavicatalytic nanoparticles due to their ability to reduce the cavitation threshold of their surrounding media without being destroyed themselves. Finally, an entirely nanoscale release system was developed and tested <em>in vitro</em> and <em>in vivo</em>. The drug carrier (the liposome) and effector agent (the cavicatalytic nanoparticle) were used to demonstrate ultrasound triggered drug release, specifically in response to the generation of cavitation events. These cavitation events could be non-invasively monitored and characterised, adding to the potential clinical utility of the technologies developed and described here.</p> |
| spellingShingle | Medical Sciences Nano-biotechnology Oncology High Intensity Focussed Ultrasound (HIFU) Biomedical engineering Nanomaterials Engineering & allied sciences Nanostructures Life Sciences Graham, S Susan M Graham Ultrasound-triggered drug release from liposomes using nanoscale cavitation nuclei |
| title | Ultrasound-triggered drug release from liposomes using nanoscale cavitation nuclei |
| title_full | Ultrasound-triggered drug release from liposomes using nanoscale cavitation nuclei |
| title_fullStr | Ultrasound-triggered drug release from liposomes using nanoscale cavitation nuclei |
| title_full_unstemmed | Ultrasound-triggered drug release from liposomes using nanoscale cavitation nuclei |
| title_short | Ultrasound-triggered drug release from liposomes using nanoscale cavitation nuclei |
| title_sort | ultrasound triggered drug release from liposomes using nanoscale cavitation nuclei |
| topic | Medical Sciences Nano-biotechnology Oncology High Intensity Focussed Ultrasound (HIFU) Biomedical engineering Nanomaterials Engineering & allied sciences Nanostructures Life Sciences |
| work_keys_str_mv | AT grahams ultrasoundtriggereddrugreleasefromliposomesusingnanoscalecavitationnuclei AT susanmgraham ultrasoundtriggereddrugreleasefromliposomesusingnanoscalecavitationnuclei |