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Sonosensitive nanoparticle formulations for cavitation-mediated ultrasonic enhancement of local drug delivery

Published online by Cambridge University Press:  07 March 2011

Sarah J. Wagstaffe ,
Manish Arora ,
Constantin-C Coussios  and
Heiko A. Schiffter
Sarah J. Wagstaffe
Affiliation:
Institute of Biomedical Engineering, Oxford University, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ
Manish Arora
Affiliation:
Institute of Biomedical Engineering, Oxford University, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ
Constantin-C Coussios
Affiliation:
Institute of Biomedical Engineering, Oxford University, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ
Heiko A. Schiffter
Affiliation:
Institute of Biomedical Engineering, Oxford University, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ
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Abstract

Inertial cavitation, namely the rapid expansion and subsequent violent collapse of micron-sized cavities under the effect of ultrasound-induced pressure variations, has widely been considered as an undesirable phenomenon for in-vivo biomedical applications. This is mainly because of its highly stochastic nature and difficulties in its reliable initiation in vivo using moderate ultrasound pressure levels. Methods of lowering the pressure required to initiate cavitation, which is known as the cavitation threshold, has been previously addressed with the use of ultrasound contrast agents in form of encapsulated stabilized micron sized bubbles. However, such agents do not readily extravasate into tumours and other target tissues due to their relatively large size. This paper investigates the engineering of core-shell nanoparticles and examines their ability to initiate inertial cavitation in the context of ultrasound-enhanced local drug delivery. The nanoparticulate formulations are size-engineered to target tumour vasculature whilst presenting high surface roughness, facilitating surface air entrapment upon drying. The core-shell nanoparticles have been demonstrated to substantially lower the cavitation threshold in aqueous solution, allowing the initiation of inertial cavitation with moderate ultrasound amplitudes and the low energy levels typically deployed by diagnostic systems. The peak focal pressure where the probability of cavitation is greater than 0.5 was found to decrease by factors of five to ten fold, dependant on particle size, total surface area and surface morphology.

Keywords

acousticnanoscalebiomedical
Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 1316: Symposium QQ – Nanofunctional Materials, Nanostructures and Nanodevices for Biomedical Applications II , 2011 , mrsf10-1316-qq05-07
Copyright
Copyright © Materials Research Society 2011

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References

REFERENCES

1. Mitragotri, S., Blankschtein, D., and Langer, R., Ultrasound-mediated transdermal protein delivery . Science (New York, N.Y.), 1995. 269(5225): p. 850–3.Google Scholar
2. Ferrari, M., et al. ., Transdermal Drug Delivery using Low-Frequency Sonophoresis, in BioMEMS and Biomedical Nanotechnology. 2007, Springer US. p. 223–236.Google Scholar
3. Mitragotri, S. and Kost, J., Low-frequency sonophoresis: a review . Adv. Drug. Delivery. Rev, 2004. 56: p. 589–601.Google Scholar
4. Rapoport, N.Y., et al. ., Ultrasound-triggered drug targeting of tumors in vitro and in vivo . Ultrasonics, 2004. 42(1–9): p. 943–950.Google Scholar
5. Daffertshofer, M. and Hemerici, M., Ultrasound in the treatment of ischaemic stroke . Lancet Neurol, 2003. 2: p. 283–290.Google Scholar
6. Kennedy, J.E., G.R., ter Haar, and D., Cranston, High intensity focused ultrasound: surgery of the future? Br J Radiol, 2003. 76(909): p. 590–599.Google Scholar
7. Husseini, G., et al. ., The role of cavitation in acoustically activated drug delivery . J Control Release, 2005. 107(2): p. 253–261.Google Scholar
8. Ng, K.-y. and Liu, Y., ChemInform Abstract: Therapeutic Ultrasound: Its Application in Drug Delivery. ChemInform, 2002. 33(21): p. no-no.Google Scholar
9. Mitragotri, S., Healing sound: the use of ultrasound in drug delivery and other therapeutic applications. Nat Rev Drug Discov, 2005. 4(3): p. 255–260.Google Scholar
10. Postema, M., et al. ., Ultrasound-induced encapsulated microbubble phenomena . Ultrasound Med Biol, 2004. 30(6): p. 827–840.Google Scholar
11. Bohmer, M., et al. ., Ultrasound triggered image-guided drug delivery . European Journal of Radiology, 2009. 70: p. 242–253.Google Scholar
12. Ferrara, K., Pollard, R., and Borden, M., Ultrasound microbubble contrast agents: fundamentals and application to drug and gene delivery . Annual Rev. Biomed. Eng., 2007. 9: p. 415–447.Google Scholar
13. Pitt, W., Husseini, G., and Staples, B., Ultrasonic Drug Delivery - A General Review . Expert Opin. Drug Deliv., 2004. 1(1): p. 37–56.Google Scholar
14. Somaglino, L., et al. ., Validation of an acoustic cavitation dose with hydroxyl radical production generated by inertial cavitation in pulsed mode: Application to in vitro drug release from liposomes . Ultrasonics Sonochemistry, 2010.Google Scholar
15. Brigger, I., Dubernet, C., and Couvreur, P., Nanoparticles in cancer therapy and diagnosis . Advanced Drug Delivery Reviews, 2002. 54(5): p. 631–651.Google Scholar
16. Schiffter, H., Manhas, V., and Arora, M., Biodegradable micro- and nanoparticles for controlled cavitation inception in water and porcine blood. Particles 2010. Orlando, Fl (USA): p. 22–26 May 2010.Google Scholar
17. Arora, M., et al. ., Biocompatible Solid Particles for Controlled Instigation of Cavitation during Therapeutic Ultrasound . J. Acoust. Soc. Am., 2010. 2010.Google Scholar
18. Caruso, F., Nanoengineering of Particle Surfaces . Adv. Mater., 2001. 13(1): p. 11–22.Google Scholar
19. Caruso, F., et al. ., Electrostatic Self-Assembly of Silica Nanoparticle-Polyelectrolyte Multilayers on Polystyrene Latex Particles. J. Am. Chem. Soc., 1998. 120: p. 8523–8524.Google Scholar