Oil-filled polymer microcapsules for ultrasound-mediated delivery of lipophilic drugs

Klazina Kooiman*, Marcel R. Böhmer*, Marcia Emmer, Hendrik J. Vos, Ceciel Chlon, William T. Shi, Christopher S. Hall, Suzanne H.P.M. de Winter, Karin Schroën, Michel Versluis, Nico de Jong, Annemieke van Wamel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

107 Citations (Scopus)
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The use of ultrasound contrast agents as local drug delivery systems continues to grow. Current limitations are the amount of drug that can be incorporated as well as the efficiency of drug release upon insonification. This study focuses on the synthesis and characterisation of novel polymeric microcapsules for ultrasound-triggered delivery of lipophilic drugs. Microcapsules with a shell of fluorinated end-capped poly(l-lactic acid) were made through pre-mix membrane emulsification and contained, apart from a gaseous phase, different amounts of hexadecane oil as a drug-carrier reservoir. Mean number weighted diameters were between 1.22 µm and 1.31 µm. High-speed imaging at ~ 10 million fames per second showed that for low acoustic pressures (1 MHz, 0.24 MPa) microcapsules compressed but remained intact. At higher diagnostic pressures of 0.51 MPa, microcapsules cracked, thereby releasing the encapsulated gas and model lipophilic drug. Using conventional ultrasound B-mode imaging at a frequency of 2.5 MHz, a marked enhancement of scatter intensity over a tissue-mimicking phantom was observed for all differently loaded microcapsules. The partially oil-filled microcapsules with high drug loads and well-defined acoustic activation thresholds have great potential for ultrasound-triggered local delivery of lipophilic drugs under ultrasound image-guidance.
Original languageEnglish
Pages (from-to)109-118
Number of pages10
JournalJournal of controlled release
Issue number2
Publication statusPublished - 2009


  • Polymer-shelled microcapsule
  • Lipophilic drug
  • Acoustic properties
  • Drug delivery
  • Ultrasound contrast agent


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