@entity1499 ( @entity1500 ) is the single most effective agent for the treatment of @entity149 . Currently, the delivery of @entity1500 to the brain is achieved by high systemic doses, which cause severe long-term @entity2359 , or intrathecal administration, which is highly invasive and may lead to @entity548 . Acoustically active microbubbles have been developed as drug carriers for the noninvasive and brain-targeted delivery of therapeutics. However, their application is limited by their low drug-loading capacity. To overcome this limitation, we prepared microbubbles coupled to @entity1500 -loaded liposomes using ZHIFUXIAN, a novel type of microbubbles with a superior safety profile and long circulation time. @entity1500 -liposome-coupled microbubbles had a high drug-loading capacity of 8.91%   0.86%, and their size (2.64    0.93  m in diameter) was suitable for intravenous injection. When used with ultrasound, they showed more potent in vitro cytotoxicity against Walker-256 @entity5 cells than @entity1500 alone or @entity1500 -loaded liposomes. When @entity35 were exposed to sonication, administration of these @entity1500 -liposome-coupled microbubbles via the tail vein led to targeted disruption of the blood-brain barrier without noticeable tissue or @entity16 . High-performance liquid chromatography analysis of the brain @entity1500 concentration showed that @entity1500 delivery to the brain followed the order of @entity1500 -liposome-coupled microbubbles + ultrasound (25.3    2.4  g/g) > unmodified ZHIFUXIAN + @entity1500 + ultrasound (18.6    2.2  g/g) > @entity1500 alone (6.97    0.75  g/g) > @entity1500 -liposome-coupled microbubbles (2.92    0.39  g/g). Therefore, treatment with @entity1500 -liposome-coupled microbubbles and ultrasound resulted in a significantly higher brain @entity1500 concentration than all other treatments (P<0.01). These results suggest that @entity1500 -liposome-coupled microbubbles may hold great promise as new and effective therapies for @entity149 and other central nervous system @entity5 .

Microbubbles coupled to @entity1499 -loaded liposomes for ultrasound-mediated delivery of XXXX across the blood-brain barrier.

@entity548 :: ('MESH:D006470', 'Disease') :: ['infections or hemorrhagic complications'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer', 'malignancies'] @entity16 :: ('MESH:D009422', 'Disease') :: ['capillary damage'] @entity149 :: ('MESH:D002493', 'Disease') :: ['primary central nervous system lymphoma'] @entity1500 :: ('CHEBI:44185', 'Chemical') :: ['MTX'] @entity35 :: ('10116', 'Species') :: ['Sprague-Dawley rats'] @entity1499 :: ('MESH:D008727', 'Chemical') :: ['Methotrexate'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity']
@entity1499 :: (MESH:D008727,Chemical) :: ['methotrexate']
