Pressure-sensitive multivesicular liposomes as a smart drug-delivery system for high-altitude pulmonary edema

Changes in bodily fluid pressures, such as pulmonary artery pressure, play key roles in high-altitude pulmonary edema (HAPE) and other disorders. Smart delivery systems releasing a drug in response to these pressures might facilitate early medical interventions. However, pressure-responsive delivery systems are unavailable. We here constructed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) based on the incomplete filling of the internal vesicle space with neutral lipids. These liposomes were loaded with amlodipine besylate (AB), a nextgeneration calcium channel inhibitor, to treat HAPE on time. AB-loaded PSMVLs (AB-PSMVLs) were destroyed, and AB was released through treatment under hydrostatic pressure of at least 25 mmHg. At 25 mmHg, which is the minimum pulmonary artery pressure value in HAPE, 38.8% of AB was released within 1 h. In a mouse HAPE model, AB-PSMVLs concentrated in the lung and released AB to diffuse into the vascular wall. Intravenously injected AB-PSMVLs before HAPE modeling resulted in a stronger protection of lung tissues and respiratory function and lower occurrence of pulmonary edema than treatment with free drug or non-pressure-sensitive ABloaded liposomes. This study offers a new strategy for developing smart drug delivery systems that respond to changes in bodily fluid pressures.

Automated summary

Changes in bodily fluid pressures are crucial in diseases like high-altitude pulmonary edema (HAPE). Researchers have developed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) that can release drugs in response to pressure changes, with potential applications in HAPE treatment. Animal experiments showed that this system provides better protection for lung tissues and respiratory function, reducing the occurrence of pulmonary edema.