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Design of Gadoteridol-Loaded Cationic Liposomal Adjuvant CAF01 for MRI of Lung Deposition of Intrapulmonary Administered Particles
journal contribution
posted on 2019-10-03, 17:35 authored by Aneesh Thakur, Fabrice Rose, Shaquib Rahman Ansari, Palle Koch, Veronica Martini, Sofie Lillelund Ovesen, Bjørn Quistorff, Samuel Maritim, Fahmeed Hyder, Peter Andersen, Dennis Christensen, Yuki Mori, Camilla FogedDesigning
effective and safe tuberculosis (TB) subunit vaccines
for inhalation requires identification of appropriate antigens and
adjuvants and definition of the specific areas to target in the lungs.
Magnetic resonance imaging (MRI) enables high spatial resolution,
but real-time anatomical and functional MRI of lungs is challenging.
Here, we describe the design of a novel gadoteridol-loaded cationic
adjuvant formulation 01 (CAF01) for MRI-guided vaccine delivery of
the clinically tested TB subunit vaccine candidate H56/CAF01. Gadoteridol-loaded
CAF01 liposomes were engineered by using a quality-by-design approach
to (i) increase the mechanistic understanding of formulation factors
governing the loading of gadoteridol and (ii) maximize the loading
of gadoteridol in CAF01, which was confirmed by cryotransmission electron
microscopy. The encapsulation efficiency and loading of gadoteridol
were highly dependent on the buffer pH due to strong attractive electrostatic
interactions between gadoteridol and the cationic lipid component.
Optimal gadoteridol loading of CAF01 liposomes showed good in vivo
stability and safety upon intrapulmonary administration into mice
while generating 1.5-fold MRI signal enhancement associated with approximately
30% T1 relaxation change. This formulation
principle and imaging approach can potentially be used for other mucosal
nanoparticle-based formulations, species, and lung pathologies, which
can readily be translated for clinical use.
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mucosal nanoparticle-based formulationslung pathologiesCAF 01 liposomesMagnetic resonance imagingquality-by-design approachnovel gadoteridol-loaded cationic adjuvant formulation 01imaging approachcationic lipid componentIntrapulmonary Administered Particles Designingsubunit vaccinesMRI signal enhancementMRI-guided vaccine deliveryvivo stabilityLung Depositionformulation principlecryotransmission electron microscopyOptimal gadoteridol loadingGadoteridol-Loaded Cationic Liposomal Adjuvant CAF 01formulation factorsTBbuffer pHencapsulation efficiency
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