Prolonged retention of liposomes in the pleural cavity of normal mice and high tumor distribution in mice with malignant pleural effusion, after intrapleural injection

Our plain-English summary of Prolonged retention of liposomes in the pleural cavity of normal mice and high tumor distribution in mice with malignant pleural effusion, after intrapleural injection, by A. Marazioti, K. Papadia, A. Giannou, et al (International Journal of Nanomedicine, 2019).

The study

• Authors: A. Marazioti, K. Papadia, A. Giannou, G.T. Stathopoulos, S.G. Antimisiaris
• Journal: International Journal of Nanomedicine
• Published: 2019;14:3773-3784
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Intrapleural administration of compounds is a lung targeted, innovative therapeutic strategy for mesothelioma, which can be refined as a route for drug delivery that minimizes the potential for systemic toxicity. However, little is currently known about the retention of liposomal drugs at the site, after such topical administration. Purpose: To evaluate the retention of liposomes in lungs following intrapleural injection, and how this might be modulated by liposome properties and disease progression. Methods: DiR-incorporating liposomes with various lipid compositions and sizes were prepared, characterized (for size distribution and zeta potential) and injected intrapleurally in normal mice and mice with malignant pleural effusion (MPE). DiR retention in pleural cavity was followed by biofluorescence imaging. Results: Experimental results demonstrate that liposome size and PEG-coating, have a significant effect on residence time in the pleural cavity; negative surface charge does not. More than 20% liposomal-DiR is retained 24 d post-injection (in some cases), indicating the high potential towards localized diseases. Ex-vivo liposomal-DiR signal in tumors of MPE mice was similar to signal in liver, suggesting high tumor targeting potential of intrapleurally injected liposomes. Finally, no difference was noticed in liposomal-DiR retention between tumor-inoculated (MPE) and healthy mice, indicating the stability of liposomes in the presence of effusion (in MPE mice). Conclusion: The current study provides novel insights for using liposomes by intrapleural administration for the treatment of lung diseases.

In plain English

This was a laboratory study in mice. It involved no people and no asbestos. The authors tested how long liposomes (tiny fat-based drug carriers) tagged with a fluorescent dye (DiR) stayed in the chest (pleural) cavity after injection. In FVB mice they compared liposomes of different sizes, with or without negative surface charge, and with or without a PEG coating, tracking the dye by imaging. Size had a significant effect (P=0.043): the large multilamellar liposomes were retained in lower amounts than small unilamellar ones. PEG-coated small liposomes were practically retained for the full 4.5 days monitored. Adding negative charge made no significant difference. At a higher dose, more than 20% of the dye remained 24 days after injection. In C57BL/6 mice with chest-cavity tumors from colon cancer cells and malignant pleural effusion (fluid build-up), PEG-coated small liposomes, followed up to 8 days, cleared in an identical pattern to healthy littermates. Dye signal in the tumors was similar to that in the liver. The authors concluded that liposomes showed sustained retention at the injection site, even with effusion, and high tumor targeting efficiency.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment (mice) testing retention of dye-labelled liposomes after injection into the pleural cavity
• Who was studied: FVB mice (3 or 4 per group); C57BL/6 mice with malignant pleural effusion induced by MC38 colon adenocarcinoma cells (n=8) and their healthy littermates; mice bred at the University of Patras, Greece
• Exposure: No asbestos exposure was studied. Mice received intrapleural injections of DiR-labelled liposomes: multilamellar (about 3.3 µm), small unilamellar (138 to 220 nm), and dehydration-rehydration vesicles (about 400 nm). Lipid compositions were DSPC/Chol, DSPC/DSPG/Chol (negatively charged) or DSPC/Chol/PEG. Doses were 150 µg or 2 mg of liposomal lipid per mouse.
• Main results:
  • In FVB mice, liposome size significantly affected retention (P=0.043); lower amounts were retained with the large MLV liposomes than with SUV liposomes
  • In FVB mice, PEG-coated SUV liposomes were practically retained for the full 4.5 days. This differed significantly from DSPC/Chol SUV (P=0.0154) and DSPC/DSPG/Chol SUV (P<0.0001).
  • In FVB mice, adding negative charge (DSPG) did not significantly change retention (P>0.05 over 4.5 d; P=0.1598 in the 24-day experiment)
  • In FVB mice given 2 mg of DRV liposomes, more than 20% of the injected dose was retained after 24 days for both lipid compositions
  • Tumor-bearing (MPE) mice and healthy littermates injected with PEG-coated SUV liposomes were imaged up to 8 days after injection
  • With PEG-coated SUV liposomes (the only type tested in this comparison), clearance from the pleural cavity followed an identical pattern in mice with malignant pleural effusion and in healthy wild-type littermates
  • In mice with malignant pleural effusion, the post-mortem dye signal in pleural tumors was similar to that in the liver
  • In healthy littermates, the post-mortem dye signal in the lungs was about 5 times lower than in the liver
  • No pleural adhesion was observed in FVB mice during or after the injections
• The authors' conclusion: The authors concluded that liposomes showed sustained retention at the injection site after intrapleural injection, even with malignant pleural effusion, and high tumor targeting efficiency. They suggested a potential for treating localized diseases, provided drug release from the liposomes is appropriately controlled.
• Limitations the authors state:
  • Monitoring of tumor-bearing mice could not be extended further because of disease progression
  • The authors were not sure that imaging signals could be accurately compared between the two mouse strains (white FVB and black BL/6)
  • DRV and SUV results could not be directly compared because different time points were used
  • The higher lung signal in tumor-bearing mice may reflect tumor invasion into the lungs and different harvest times (day 10 versus day 24)
  • The dye tracks the liposomes, not a drug; for actual drugs, retention of the drug inside the liposomes will also matter

Topics

Medical terms in this study, explained in our Lexicon: Pleural Cavity, Pleural Effusion, Mesothelioma, Disease Progression.

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