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PLGA Nanoparticles Formed by Single- or Double-emulsion with Vitamin E-TPGS
Published on: December 27, 2013
PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and
Frantiescoli Anversa Dimer1, Cristiane de Souza Carvalho-Wodarz1, Adriely Goes2
1Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Saarbrücken, Germany.
Abstract:
Drug delivery systems are promising for targeting antibiotics directly to infected tissues. To reach intracellular Staphylococcus aureus and Mycobacterium abscessus, we encapsulated clarithromycin in PLGA nanocapsules, suitable for aerosol delivery by nebulization of an aqueous dispersion. Compared to the same dose of free clarithromycin, nanoencapsulation reduced 1000 times the number of intracellular S. aureus in vitro. In RAW cells, while untreated S. aureus was located in acidic compartments, the treated ones were mostly situated in non-acidic compartments. Clarithromycin-nanocapsules were also effective against M. abscessus (70-80% killing efficacy). The activity of clarithromycin-nanocapsules against S. aureus was also confirmed in vivo, using a murine wound model as well as in zebrafish. The permeability of clarithromycin-nanocapsules across Calu-3 monolayers increased in comparison to the free drug, suggesting an improved delivery to sub-epithelial tissues. Thus, clarithromycin-nanocapsules are a promising strategy to target intracellular S. aureus and M. abscessus.
Insights
Novel nanocapsules effectively deliver clarithromycin to target intracellular Staphylococcus aureus and Mycobacterium abscessus infections. This antibiotic drug delivery system shows significant potential for treating challenging bacterial infections.
Area of Science:
- Pharmacology
- Nanotechnology
- Infectious Diseases
Background:
- Drug delivery systems offer targeted antibiotic delivery to infection sites.
- Intracellular pathogens like Staphylococcus aureus and Mycobacterium abscessus pose treatment challenges.
Purpose of the Study:
- To develop and evaluate PLGA nanocapsules for aerosol delivery of clarithromycin.
- To assess the efficacy of nanoencapsulated clarithromycin against intracellular S. aureus and M. abscessus.
Main Methods:
- Encapsulation of clarithromycin in PLGA nanocapsules for aerosolization.
- In vitro testing against intracellular S. aureus and M. abscessus in cell cultures.
- In vivo studies using a murine wound model and zebrafish.
- Assessment of drug permeability across Calu-3 cell monolayers.
Main Results:
- Nanoencapsulation reduced intracellular S. aureus by 1000-fold compared to free clarithromycin.
- Clarithromycin nanocapsules demonstrated 70-80% killing efficacy against M. abscessus.
- In vivo studies confirmed efficacy against S. aureus.
- Improved permeability of nanocapsules suggests enhanced delivery to sub-epithelial tissues.
Conclusions:
- Clarithromycin-loaded PLGA nanocapsules are a promising strategy for targeting intracellular S. aureus and M. abscessus.
- Aerosol delivery of nanoencapsulated clarithromycin enhances antibiotic efficacy.
- This approach may overcome limitations of conventional antibiotic treatments for intracellular infections.
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