4 research outputs found
Supramolecular structures based on regiosisomers of cinnamyl-α-cyclodextrins - new media for capillary separation techniques
This work focuses on the preparation and application of supramolecular structures based on mono-cinnamyl-α-cyclodextrins (Cin-α-CD). Pure regioisomers of Cin-α-CD having the cinnamyl moiety at the 2-O- or at the 3-O-position, respectively, were prepared, characterized and applied in capillary electrophoresis as additives to the background electrolyte. These new monomer units with a potential to self-organize into supramolecular structures were synthesized via a straightforward one-step synthetic procedure and purified using preparative reversed-phase chromatography allowing a large scale separation of the regioisomers. The ability of the monomers to self-assemble was proved by various methods including NMR spectroscopy and dynamic light scattering (DLS). The light scattering experiments showed that the monomer units have distinguishable ability to form supramolecular structures in different solvents and the size distribution of the aggregates in water can be easily modulated using different external stimuli, such as temperature or competitive guest molecules. The obtained results indicated that the two regioisomers of Cin-α-CD formed different supramolecular assemblies highlighting the fact that the position of the cinnamyl group plays an important role in the intermolecular complex formation
Widening the Therapeutic Perspectives of Clofazimine by Its Loading in Sulfobutylether \u3b2-Cyclodextrin Nanocarriers: Nanomolar IC50Values against MDR S. epidermidis
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-\u3b2-cyclodextrins for CLZ loading. A new oligomeric carrier was obtained cross-linking \u3b2CyD 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 \u3bcM, 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
Cyclodextrin-mesoporous silica particle composites for controlled antibiotic release. A proof of concept toward colon targeting
Cyclodextrins (CDs) and mesoporous silica particles (MSPs) have been combined as composite carriers for controlled antibiotic release. CDs were employed as "gatekeeper" agents and grafted onto MSPs to retain drug molecules inside the MSP carrier. A variety of CDs (unfunctionalized, positively charged and carboxymethylated) and three different coupling strategies (covalent binding, electrostatic adsorption and inclusion complexation) were systematically investigated for their ability to control the release of two antibiotic drugs, metronidazole and clofazimine. The drugs had significantly different physicochemical properties (metronidazole - small hydrophilic, clofazimine- large hydrophobic). We report for the first time on the encapsulation and characterization of metronidazole-loaded-MSP. Each CD coating strategy reduced the drug release rate in phosphate buffer compared to unmodified MSP (from 20% to 100% retained drug). Covalent binding and inclusion complex approaches were significantly more effective than electrostatically adsorbed CD. In particular, the novel inclusion complex based on host/guest interaction between benzyl-modified silica surface and alpha-CD proved to be very effective (60-100% retained drug amount). Using pharmaceutical manufacturing processes, our study shows that CD-MSP composites can retain both hydrophobic and hydrophilic antibiotic compounds with potential translation to triggered release formulation targeting bacterial infections in the colon and lower intestine
Widening the Therapeutic Perspectives of Clofazimine by Its Loading in Sulfobutylether β‑Cyclodextrin Nanocarriers: Nanomolar IC<sub>50</sub> Values against MDR <i>S. epidermidis</i>
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 IC<sub>50</sub> values below 100 nM against <i>S. epidermidis</i>. The same holds true also for clinical isolates
of <i>S. epidermidis</i>, 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