BACKGROUND: Many aspects of the mechanisms involved in ultrasound-mediated therapy remain obscure. In particular, the relative roles of drug and ultrasound, the effect of the time of ultrasound application, and the effect of tissue heating are not yet clear. The current study was undertaken with the goal to clarify these aspects of the ultrasound-mediated drug delivery mechanism. METHODS: Focused ultrasound-mediated drug delivery was performed under magnetic resonance imaging guidance (MRgFUS) in a @entity1124 ( @entity1124 ) model grown subcutaneously in nu/nu @entity19 . @entity1311 (PTX) was used as a chemotherapeutic agent because it manifests high potency in the treatment of @entity136 -resistant @entity1124 . Poly(ethylene oxide)-co-poly(d,l-lactide) block copolymer stabilized @entity54169 nanoemulsions were used as drug carriers. MRgFUS was applied at sub-ablative pressure levels in both continuous wave and pulsed modes, and only a fraction of the @entity5 was treated. RESULTS: Positive treatment effects and even complete @entity5 resolution were achieved by treating the @entity5 with MRgFUS after injection of nanodroplet encapsulated drug. The MRgFUS treatment enhanced the action of the drug presumably through enhanced @entity5 perfusion and blood vessel and cell membrane permeability that increased the drug supply to @entity5 cells. The effect of the pulsed MRgFUS treatment with PTX-loaded nanodroplets was clearly smaller than that of continuous wave MRgFUS treatment, supposedly due to significantly lower temperature increase as measured with MR thermometry and decreased extravasation. The time of the MRgFUS application after drug injection also proved to be an important factor with the best results observed when ultrasound was applied at least 6 h after the injection of drug-loaded nanodroplets. Some collateral damage was observed with particular ultrasound protocols supposedly associated with enhanced @entity32 . CONCLUSION: This presented data suggest that there exists an optimal range of ultrasound application parameters and drug injection time. @entity5 growth, or complete resolution, was achieved with continuous wave ultrasound pressures below or equal to 3.1 MPa and drug injection times of at least 6 h prior to treatment. Increased acoustic pressure or ultrasound application before or shortly after drug injection gave increased @entity5 growth when compared to other protocols.

Focused ultrasound-mediated drug delivery to pancreatic cancer in a XXXX model.

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity54169 :: ('MESH:C089317', 'Chemical') :: ['perfluoro-15-crown-5-ether'] @entity1124 :: ('MESH:D021441', 'Disease') :: ['PDA', 'pancreatic ductal adenocarcinoma'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Decreased tumor'] @entity1311 :: ('MESH:D017239', 'Chemical') :: ['Paclitaxel'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['gemcitabine']
@entity19 :: (10090,Species) :: ['mouse']
