title: Polymeric microbubbles as delivery vehicles for sensitizers in sonodynamic therapy.
abstract: Microbubbles (MBs) have recently emerged as promising delivery vehicles for sensitizer drugs in sonodynamic therapy (SDT). The ability to selectively destroy the MB and activate the sensitizer using an external ultrasound trigger could provide a minimally invasive and highly targeted therapy. While lipid MBs have been approved for use as contrast agents in diagnostic ultrasound, the attachment of sensitizer drugs to their surface results in a significant reduction in particle stability. In this Article, we prepare both lipid and polymer (PLGA) MBs with rose bengal attached to their surface and demonstrate that PLGA MB conjugates are significantly more stable than their lipid counterparts. In addition, the improved stability offered by the PLGA shell does not hinder their selective destruction using therapeutically acceptable ultrasound intensities. Furthermore, we demonstrate that treatment of ectopic human tumors (BxPC-3) in mice with the PLGA MB-rose bengal conjugate and ultrasound reduced tumor volume by 34% 4 days after treatment while tumors treated with the conjugate alone increased in volume by 48% over the same time period. Therefore, PLGA MBs may offer a more stable alternative to lipid MBs for the site specific delivery of sensitizers in SDT.
authors.affiliation: Biomedical Sciences Research Institute, University of Ulster , Coleraine, Northern Ireland BT52 1SA, United Kingdom.
authors.forename: Conor
authors.initials: C
authors.lastname: McEwan
authors.forename: Colin
authors.initials: C
authors.lastname: Fowley
authors.forename: Nikolitsa
authors.initials: N
authors.lastname: Nomikou
authors.forename: Bridgeen
authors.initials: B
authors.lastname: McCaughan
authors.forename: Anthony P
authors.initials: AP
authors.lastname: McHale
authors.forename: John F
authors.initials: JF
authors.lastname: Callan
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003374:Coumarins; D016503:Drug Delivery Systems; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D045423:Microbubbles; D015394:Molecular Structure; D014464:Ultrasonic Therapy; D014465:Ultrasonics; D014594:Uterine Neoplasms / Q000628:therapy
chemical_list: D003374:Coumarins; C030123:coumarin