The effect of high intensity focussed ultrasound (HIFU) on pH responsive PEGylated micelles.

Chemical Engineering Department, Cambridge University, New Museums Site, CB2 3RA Cambridge, UK, .
The Journal of the Acoustical Society of America (Impact Factor: 1.65). 06/2008; 123(5):3223. DOI: 10.1121/1.2933428
Source: PubMed

ABSTRACT The effect of HIFU on pH responsive PEGylated micelles was investigated. Micelles can be used as drug carrier vehicles reducing unwanted drug toxicity. HIFU is able to release drugs from the circulating micelles, as well as improving intracellular uptake of both micelle-encapsulated and free drugs non-invasively. Large molecules generally enter cells by endocytosis. Endosomes gradually become acidic and fuse with enzyme containing lysosomes degrading the endosomal contents and preventing them from reaching their intracellular target. Using pH responsive polymers enables endosomes to be distrupted, releasing their contents into the cytoplasm before degradation occurs. Addition of poly(ethylene glycol), referred to as PEGylation, prolongs circulatory half-life and reduces degradation within the bloodstream. HIFU did enable release of encapsulated molecules from the modified micelles, and the micelles were taken up by H69 human carcinoma cells in vitro. Further work will investigate optimization of the micelles to maximize encapsulated drug release. The combined approach of using both pH responsive PEGylated micelles and HIFU to deliver drugs would provide more accurate targeting of therapies allowing higher therapeutic doses to be administered, reduce unwanted side effects and give patients a higher quality of life.

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