Dataset Information

An optical and microPET assessment of thermally-sensitive liposome biodistribution in the Met-1 tumor model: Importance of formulation.

ABSTRACT: The design of delivery vehicles that are stable in circulation but can be activated by exogenous energy sources is challenging. Our goals are to validate new imaging methods for the assessment of particle stability, to engineer stable and activatable particles and to assess accumulation of a hydrophilic model drug in an orthotopic tumor. Here, liposomes were injected into the tail vein of FVB mice containing bilateral Met-1 tumors and imaged in vivo using microPET and optical imaging techniques. Cryo-electron microscopy was applied to assess particle shape prior to injection, ex vivo fluorescence images of dissected tissues were acquired, excised tissue was further processed with a cell-digest preparation and assayed for fluorescence. We find that for a stable particle, in vivo tumor images of a hydrophilic model drug were highly correlated with PET images of the particle shell and ex vivo fluorescence images of processed tissue, R(2)=0.95 and R(2)=0.99 respectively. We demonstrate that the accumulation of a hydrophilic model drug is increased by up to 177 fold by liposomal encapsulation, as compared to accumulation of the drug at 24 hours.

SUBMITTER: Paoli EE

PROVIDER: S-EPMC2861564 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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An optical and microPET assessment of thermally-sensitive liposome biodistribution in the Met-1 tumor model: Importance of formulation.

Paoli E E EE Kruse D E DE Seo J W JW Zhang H H Kheirolomoom A A Watson K D KD Chiu P P Stahlberg H H Ferrara K W KW

Journal of controlled release : official journal of the Controlled Release Society 20091216 1

The design of delivery vehicles that are stable in circulation but can be activated by exogenous energy sources is challenging. Our goals are to validate new imaging methods for the assessment of particle stability, to engineer stable and activatable particles and to assess accumulation of a hydrophilic model drug in an orthotopic tumor. Here, liposomes were injected into the tail vein of FVB mice containing bilateral Met-1 tumors and imaged in vivo using microPET and optical imaging techniques. ...[more]

PMID: 20006659

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Project description:This study sheds light on the biodistribution of orally administered, liposome-encapsulated bacteriophages, and their transcytosis through intestinal cell layers. Fluorochrome-labeled bacteriophages were used together with a non-invasive imaging methodology in the in vivo visualization of bacteriophages in the stomach and intestinal tract of mice. In those studies, phage encapsulation resulted in a significant increase of the labeled phages in the mouse stomach, even 6 h after their oral administration, and without a decrease in their concentration. By contrast, the visualization of encapsulated and non-encapsulated phages in the intestine were similar. Our in vivo observations were corroborated by culture methods and ex vivo experiments, which also showed that the percentage of encapsulated phages in the stomach remained constant (50%) compared to the amount of initially administered product. However, the use of conventional microbiological methods, which employ bile salts to break down liposomes, prevented the detection of encapsulated phages in the intestine. The ex vivo data showed a higher concentration of non-encapsulated than encapsulated phages in liver, kidney, and even muscle up to 6 h post-administration. Encapsulated bacteriophages were able to reach the liver, spleen, and muscle, with values of 38% ± 6.3%, 68% ± 8.6%, and 47% ± 7.4%, respectively, which persisted over the course of the experiment. Confocal laser scanning microscopy of an in vitro co-culture of human Caco-2/HT29/Raji-B cells revealed that Vybrant-Dil-stained liposomes containing labeled bacteriophages were preferably embedded in cell membranes. No transcytosis of encapsulated phages was detected in this in vitro model, whereas SYBR-gold-labeled non-encapsulated bacteriophages were able to cross the membrane. Our work demonstrates the prolonged persistence of liposome-encapsulated phages in the stomach and their adherence to the intestinal membrane. These observations could explain the greater long-term efficacy of phage therapy using liposome-encapsulated phages.

Dataset Information

An optical and microPET assessment of thermally-sensitive liposome biodistribution in the Met-1 tumor model: Importance of formulation.

Publications

An optical and microPET assessment of thermally-sensitive liposome biodistribution in the Met-1 tumor model: Importance of formulation.

Similar Datasets

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