In vivo efficacy & phantom imaging connote the theranostic potential of a drug-loaded lipid nanobubble

Abstract

The current American College of Rheumatology (ACR) guidelines emphasize on targeting rheumatoid arthritis in its early inflammatory phase for diagnosis and intervention to be effective. Ultrasound has been implicated as an affordable non-invasive modality to assess early pathology in synovitis. Additionally, therapeutic ultrasound can be used as an effective trigger for drug delivery. Commercial ultrasound contrast agents are microbubbles which have limitations as ‘theranostic’ agents with both diagnostic and therapeutic functions. In the present study, we have reported the development of a dexamethasone loaded nanobubble (DNB) which could have dual function as a theranostic contrast agent. In-vitro echogenicity studies were carried out using phantom imaging which suggested that these nanobubbles were quite stable up to 6 months at 2–8 °C in lyophilized form and displayed echogenic signal comparable to commercial Sonovue® up to 10mins. A significant anti-inflammatory activity was observed in presence of ultrasound on Raw 264.7 and THP1 cells. In vivo efficacy studies on adjuvant induced arthritic rodent model indicated significant reduction in visible and inflammatory markers in group treated with DNBs when compared to diseased control. Overall, these DNBs when subjected to therapeutic or diagnostic ultrasound provide a triggered drug release and contrast enhancement respectively highlighting theranostic potential and thus, can be explored in future for a precision therapy in RA.