Biodistribution of pH-responsive liposomes for MRI and a novel approach to improve the pH-responsiveness

The potential of pH-sensitive paramagnetic liposomes as a probe for monitoring acidic pH in tumours with magnetic resonance imaging has recently been demonstrated. If the blood retention time is prolonged, such liposomes can accumulate in tumour interstitium due to increased vascular permeability an...

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Bibliographic Details
Published in:Journal of controlled release 2004-07, Vol.98 (1), p.87-95
Main Authors: Løkling, Knut-Egil, Fossheim, Sigrid L, Klaveness, Jo, Skurtveit, Roald
Format: Article
Language:English
Subjects:
Animals
Biodistribution
Biological and medical sciences
Contrast agents
General pharmacology
Hydrogen-Ion Concentration
Liposomes - chemistry
Liposomes - metabolism
Magnetic Resonance Imaging - methods
Male
Medical sciences
Paramagnetic liposomes
pH-sensitivity
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Protein binding
Rats
Rats, Sprague-Dawley
Relaxivity
Tissue Distribution - drug effects
Tissue Distribution - physiology
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Summary:The potential of pH-sensitive paramagnetic liposomes as a probe for monitoring acidic pH in tumours with magnetic resonance imaging has recently been demonstrated. If the blood retention time is prolonged, such liposomes can accumulate in tumour interstitium due to increased vascular permeability and interstitial retention. In the present study, biodistribution studies in healthy rats showed rapid clearance of the pH-sensitive system dipalmitoylphosphatidylethanolamine (DPPE)/dipalmitoylglycerosuccinate (DPSG) liposomal GdDTPA-BMA from the blood circulation with most of the Gd dose in the liver at 15 min post intravenous injection. Incorporation of 1.5 mol% polyethylene glycol (PEG) grafted DPPE (DPPE-PEG) in the above-mentioned formulation resulted in a significantly prolonged blood circulation time. However, the relaxometric pH-response of the DPPE/DPSG/DPPE-PEG system decreased as a function of mol% DPPE-PEG. Therefore, a compromise would be necessary between long blood residence time and a suitable pH-sensitivity of the liposomes. A possible approach to compensate for the reduced pH-sensitivity was investigated. Gadofosveset, a low-molecular weight Gd-chelate with high affinity for albumin, was encapsulated within DPPE/DPSG liposomes. This promising system showed in blood a markedly higher relaxometric response than the corresponding system with GdDTPA-BMA, due to release of gadofosveset at low pH and subsequent binding to albumin.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2004.04.015