Low-intensity pulsed ultrasound combined with microbubbles enhances amphotericin B delivery across the blood-brain barrier for improved therapy of cryptococcal meningitis.
J, L., Z, L., D, L., J, L., Y, S., Y, L., Y, L., L, X., L, S., & X, S. (2026). Low-intensity pulsed ultrasound combined with microbubbles enhances amphotericin B delivery across the blood-brain barrier for improved therapy of cryptococcal meningitis.. Drug delivery. https://doi.org/10.1080/10717544.2026.2677305
J L, Z L, D L, J L, Y S, Y L, et al. Low-intensity pulsed ultrasound combined with microbubbles enhances amphotericin B delivery across the blood-brain barrier for improved therapy of cryptococcal meningitis.. Drug delivery. 2026; doi: 10.1080/10717544.2026.2677305
J L, Z L, D L, et al. Low-intensity pulsed ultrasound combined with microbubbles enhances amphotericin B delivery across the blood-brain barrier for improved therapy of cryptococcal meningitis.[J]. Drug delivery. 2026. DOI: 10.1080/10717544.2026.2677305.
@article{j2026,
author = {Liu J and Li Z and Li D and Liu J and Su Y and Leng Y and Li Y and Xu L and Sun L and Su X},
title = {Low-intensity pulsed ultrasound combined with microbubbles enhances amphotericin B delivery across the blood-brain barrier for improved therapy of cryptococcal meningitis.},
journal = {Drug delivery},
year = {2026},
doi = {10.1080/10717544.2026.2677305},
note = {PMID: 42241274},
}
TY - JOUR AU - Liu J AU - Li Z AU - Li D AU - Liu J AU - Su Y AU - Leng Y AU - Li Y AU - Xu L AU - Sun L AU - Su X TI - Low-intensity pulsed ultrasound combined with microbubbles enhances amphotericin B delivery across the blood-brain barrier for improved therapy of cryptococcal meningitis. T2 - Drug delivery PY - 2026 DO - 10.1080/10717544.2026.2677305 AN - PMID:42241274 ER -
Cryptococcal meningitis (CM), a life-threatening fungal infection of the central nervous system, faces therapeutic challenges due to poor blood‒brain barrier (BBB) penetration of amphotericin B. This study investigates the efficacy of low-intensity pulsed ultrasound (LIPUS) combined with microbubbles in enhancing BBB permeability and improving prognosis in a murine CM model. Our findings suggest that LIPUS combined with microbubbles treatment significantly increased BBB permeability, leading to elevated cerebral concentrations of amphotericin B and improved fungicidal activity against Cryptococcus neoformans in the brain. Mechanistic investigations revealed that LIPUS-microbubble treatment transiently upregulated vascular endothelial growth factor (VEGF) expression levels in cerebral tissues. Notably, these protein expression alterations and the associated BBB permeability enhancement completely normalized within 6 hours post-treatment. Pharmacological inhibition of VEGF abolished the ultrasound-induced BBB permeability increase, indicating that VEGF may serve as a pivotal upstream regulator mediating this transient barrier modulation. Compared with amphotericin B monotherapy, the combined regimen of LIPUS plus microbubbles and amphotericin B achieved a greater reduction in cerebral cryptococcal burden. The India ink staining revealed reduced cryptococcal capsule thickness and smaller yeast cell diameters in treated mice. Furthermore, the intervention ameliorated CM-associated clinical manifestations, including weight loss and neurological deficits, while prolonging survival time. These results suggest the potential of LIPUS-microbubble-mediated BBB modulation as a promising adjunctive strategy to optimize amphotericin B delivery and improve therapeutic efficacy in CM, offering new insights into overcoming the limitations of conventional treatments for neurotropic fungal infections.