Clofazimine (CLZ) is an antibiotic with a promising behavior against Gram-positive bacteria; however, the drug is completely insoluble in water and accumulates in fat tissues. We explored nanocarriers, labeled and not labeled with rhodamine, consisting of negatively charged sulfobutylether-β-cyclodextrins for CLZ loading. A new oligomeric carrier was obtained cross-linking βCyD with epichlorohydrin followed by sulfonation in a strongly alkaline aqueous medium. The oligomeric carrier has a MW of 53 kDa and forms small nanoparticles of a few tens of nm. With aqueous solutions containing a 25 mg/mL oligomeric carrier, we loaded up to 0.5 mg/mL of drug. The oligomers exhibited a 10-fold better loading capacity compared to monomers and formed nanoparticles with a size in the 20-60 nm range after drug loading. Circular dichroism confirmed encapsulation of the CLZ in the nanocarriers. All carriers with or without CLZ are not cytotoxic up to 1 μM, while CLZ alone is highly cytotoxic at the same concentration. The drug has IC50values below 100 nM against S. epidermidis. The same holds true also for clinical isolates of S. epidermidis, some displaying MDR. So, the selectivity index significantly increased for CLZ/carrier systems compared to the drug alone. Taken all together, our results open new avenues for the clinical application of this antibiotic.

Widening the Therapeutic Perspectives of Clofazimine by Its Loading in Sulfobutylether β-Cyclodextrin Nanocarriers: Nanomolar IC50Values against MDR S. epidermidis / Jitendra Wankar, Francesca Bonvicini,Gabor Benkovics,Valentina Marassi, Milo Malanga, Eva Fenyvesi, Giovanna Angela Gentilomi, Pierluigi Reschiglian, Barbara Roda, Ilse Manet. - In: MOLECULAR PHARMACEUTICS. - ISSN 1543-8384. - ELETTRONICO. - 15:9(2018), pp. 3823-3836. [10.1021/acs.molpharmaceut.8b00321]

Widening the Therapeutic Perspectives of Clofazimine by Its Loading in Sulfobutylether β-Cyclodextrin Nanocarriers: Nanomolar IC50Values against MDR S. epidermidis

Francesca Bonvicini;Valentina Marassi;Giovanna Angela Gentilomi;Pierluigi Reschiglian;Barbara Roda;
2018

Abstract

Clofazimine (CLZ) is an antibiotic with a promising behavior against Gram-positive bacteria; however, the drug is completely insoluble in water and accumulates in fat tissues. We explored nanocarriers, labeled and not labeled with rhodamine, consisting of negatively charged sulfobutylether-β-cyclodextrins for CLZ loading. A new oligomeric carrier was obtained cross-linking βCyD with epichlorohydrin followed by sulfonation in a strongly alkaline aqueous medium. The oligomeric carrier has a MW of 53 kDa and forms small nanoparticles of a few tens of nm. With aqueous solutions containing a 25 mg/mL oligomeric carrier, we loaded up to 0.5 mg/mL of drug. The oligomers exhibited a 10-fold better loading capacity compared to monomers and formed nanoparticles with a size in the 20-60 nm range after drug loading. Circular dichroism confirmed encapsulation of the CLZ in the nanocarriers. All carriers with or without CLZ are not cytotoxic up to 1 μM, while CLZ alone is highly cytotoxic at the same concentration. The drug has IC50values below 100 nM against S. epidermidis. The same holds true also for clinical isolates of S. epidermidis, some displaying MDR. So, the selectivity index significantly increased for CLZ/carrier systems compared to the drug alone. Taken all together, our results open new avenues for the clinical application of this antibiotic.
2018
Widening the Therapeutic Perspectives of Clofazimine by Its Loading in Sulfobutylether β-Cyclodextrin Nanocarriers: Nanomolar IC50Values against MDR S. epidermidis / Jitendra Wankar, Francesca Bonvicini,Gabor Benkovics,Valentina Marassi, Milo Malanga, Eva Fenyvesi, Giovanna Angela Gentilomi, Pierluigi Reschiglian, Barbara Roda, Ilse Manet. - In: MOLECULAR PHARMACEUTICS. - ISSN 1543-8384. - ELETTRONICO. - 15:9(2018), pp. 3823-3836. [10.1021/acs.molpharmaceut.8b00321]
Jitendra Wankar, Francesca Bonvicini,Gabor Benkovics,Valentina Marassi, Milo Malanga, Eva Fenyvesi, Giovanna Angela Gentilomi, Pierluigi Reschiglian, Barbara Roda, Ilse Manet
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/646895
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