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Interferon-gamma in starch microparticles: nitric oxide-generating activity in vitro and antileishmanial effect in
L Degling1, P Stjärnkvist, I Sjöholm
1Department of Pharmacy, Pharmaceutics, Uppsala University, Sweden.
Abstract:
Recombinant mouse interferon-gamma (mu IFN-gamma) was covalently coupled to polyacryl starch microparticles, a lysosomotropic drug carrier. The microparticle-bound mu IFN-gamma was found to activate cultured macrophages for nitrite production and had an anti-leishmanial effect in mice. Low doses of mu IFN-gamma, which had no effect in the free form, when bound to microparticles significantly reduced the load of Leishmania donovani in infected mice. Further, inducement of nitrite production in cultured macrophages by microparticle-bound mu IFN-gamma required intact cell membrane receptors.
Insights
Recombinant mouse interferon-gamma (mu IFN-gamma) bound to microparticles effectively activates macrophages and combats Leishmania donovani infections in mice, even at low doses ineffective in its free form.
Area of Science:
- Immunology
- Parasitology
- Biomaterials Science
Background:
- Recombinant mouse interferon-gamma (mu IFN-gamma) is a key cytokine involved in immune responses.
- Lysosomotropic drug carriers, such as polyacryl starch microparticles, can enhance drug delivery and efficacy.
- Leishmania donovani is a parasite responsible for visceral leishmaniasis, a serious infectious disease.
Purpose of the Study:
- To investigate the efficacy of mu IFN-gamma covalently coupled to polyacryl starch microparticles as a therapeutic agent.
- To evaluate the anti-leishmanial activity of microparticle-bound mu IFN-gamma in vivo.
- To explore the mechanism of action of microparticle-bound mu IFN-gamma in activating macrophages.
Main Methods:
- Covalent coupling of mu IFN-gamma to polyacryl starch microparticles.
- Assessment of macrophage activation via nitrite production in vitro.
- Evaluation of anti-leishmanial effects in Leishmania donovani-infected mice.
- Investigation of the role of cell membrane receptors in mu IFN-gamma-mediated macrophage activation.
Main Results:
- Microparticle-bound mu IFN-gamma activated cultured macrophages to produce nitrite.
- Microparticle-bound mu IFN-gamma demonstrated a significant anti-leishmanial effect in infected mice.
- Low doses of mu IFN-gamma, ineffective in free form, showed efficacy when bound to microparticles.
- Activation of macrophages by microparticle-bound mu IFN-gamma required intact cell membrane receptors.
Conclusions:
- Polyacryl starch microparticles serve as an effective carrier for mu IFN-gamma, enhancing its therapeutic potential.
- Microparticle-bound mu IFN-gamma offers a promising strategy for treating Leishmania donovani infections.
- The mechanism of action involves macrophage activation dependent on cell surface receptors.