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Biodistribution of long-circulating PEG-liposomes in a murine model of established subcutaneous abscesses
Lorna E T Stearne1, Raymond M Schiffelers, Edwin Smouter
1Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, P.O. Box 1738, 3000 DR, Netherlands. stearne@kmic.fgg.eur.nl
Abstract:
The biodistribution of long-circulating PEG-liposomes in a subcutaneous mouse model of established mixed infection abscesses was investigated to assess their possible role as drug carriers in the treatment of small, undrainable intra-abdominal abscesses. There was a 10-30-fold greater localisation of (67)Ga-labelled PEG-liposomes in abscesses compared to uninfected normal skin samples. Over 3% of the injected dose (ID) of liposomes was present in the abscesses 24 h after liposome administration in contrast to 0.1% in normal skin sections. The percentage ID present in the liver, spleen and kidneys was 17%, 4% and 2% per organ respectively. Five days after liposome injection, 2% ID could still be recovered from the abscesses. Using colloidal gold-labelled PEG-liposomes, it was shown that there was a 4-fold greater density of liposome clusters in the subcutaneous tissue surrounding the capsule than in the core of the abscesses. The clusters within the abscesses were distributed evenly. We conclude that PEG-liposomes localise to a significant degree at the infection focus in our mouse model and may provide a new approach to the antimicrobial treatment of intra-abdominal abscesses.
Insights
PEG-liposomes show significant accumulation in abscesses, indicating potential as drug carriers for treating intra-abdominal infections. This targeted delivery offers a promising new approach for antimicrobial therapy.
Area of Science:
- Pharmacology
- Biomedical Engineering
- Infectious Diseases
Background:
- Intra-abdominal abscesses are challenging to treat due to their location and potential for undrainable pockets.
- Conventional antimicrobial therapies may struggle to achieve sufficient drug concentrations at the infection site.
- Long-circulating liposomes offer potential for targeted drug delivery.
Purpose of the Study:
- To investigate the biodistribution of polyethylene glycol (PEG)-liposomes in a mouse model of established subcutaneous abscesses.
- To evaluate the potential of PEG-liposomes as drug carriers for treating intra-abdominal abscesses.
Main Methods:
- Utilized (67)Ga-labeled PEG-liposomes to track biodistribution in a subcutaneous abscess mouse model.
- Quantified liposome localization in abscesses compared to normal skin.
- Assessed liposome distribution in major organs (liver, spleen, kidneys).
- Employed colloidal gold-labeled PEG-liposomes to examine cluster density around and within abscesses.
Main Results:
- PEG-liposomes demonstrated 10-30 fold greater localization in abscesses compared to normal skin.
- Over 3% of the injected dose (ID) of PEG-liposomes localized to abscesses within 24 hours, persisting at 2% ID after 5 days.
- Organ distribution showed 17% ID in the liver, 4% in the spleen, and 2% in the kidneys.
- PEG-liposome clusters were more concentrated in the tissue surrounding abscess capsules than within the core.
Conclusions:
- PEG-liposomes exhibit significant localization at infection sites in a preclinical abscess model.
- These findings suggest PEG-liposomes hold promise as a novel drug delivery system for antimicrobial treatment of intra-abdominal abscesses.
