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Cyclodextrin-based metal-organic frameworks (CD-MOFs) represent an environment-friendly and biocompatible class of MOFs drawing increasing attention in drug delivery. Lansoprazole (LPZ) is a proton-pump inhibitor used to reduce the production of acid in the stomach and recently identified as an antitubercular prodrug. Herein, LPZ loaded CD-MOFs were successfully synthesized upon the assembly with γ-CD in the presence of K + ions using an optimized co-crystallization method. They were characterized in terms of morphology, size and crystallinity, showing almost perfect cubic morphologies with monodispersed size distributions. The crystalline particles, loaded or not with LPZ, have mean diameters of around 6μm. The payloads reached 23.2±2.1% (wt) which corresponds to a molar ratio of 1:1 between LPZ and γ-CD. It was demonstrated that even after two years storage, the incorporated drug inside the CD-MOFs maintained its spectroscopic characteristics. Molecular modelling provided a deeper insight into the interaction between the LPZ and CD-MOFs. Raman spectra of individual particles were recorded, confirming the formation of inclusion complexes within the tridimensional CD-MOF structures. Of note, it was found that each individual particle had the same chemical composition. The LPZ-loaded particles had remarkable homogeneity in terms of both drug loading and size. These results pave the way towards the use of CD-MOFs for drug delivery purposes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Tuberculosis (TB) remains a major global health problem. The use of ethionamide (ETH), a main second line drug, is associated to severe toxic side-effects due to its low therapeutic index. In this challenging context, "booster" molecules have been synthetized to increase the efficacy of ETH. However, the administration of ETH/booster pair is mostly hampered by the low solubility of these drugs and the tendency of ETH to crystallize. Here, ETH and a poorly water-soluble booster, so-called BDM43266, were simultaneously loaded in polymeric β-cyclodextrin nanoparticles (pβCyD NPs) following a "green" protocol. The interaction of ETH and BDM43266 with pβCyD NPs was investigated by complementary techniques. Remarkably, the inclusion of ETH and BDM43266 pβCyD NPs led to an increase of their apparent solubility in water of 10- and 90-fold, respectively. Competition studies of ETH and BDM43266 for the CyD cavities of pβCyD NPs corroborated the fact that the drugs did not compete with each other, confirming the possibility to simultaneously co-incorporate them in NPs. The drug-loaded NP suspensions could be filtered through 0.22μm filters. Finally, the drug-loaded NPs were passed through a Microsprayer ® to evaluate the feasibility to administer pβCyD NPs by pulmonary route. Each spray delivered a constant amount of both drugs and the NPs were totally recovered after passage through the Microsprayer ® . These promising results pave the way for a future use of pβCyD NPs for the pulmonary delivery of the ETH/BDM43266 pair., (Copyright © 2017. Published by Elsevier B.V.)

Ethionamide (ETH) is a second line antitubercular drug suffering from poor solubility in water and strong tendency to crystallize. These drawbacks were addressed by loading ETH in β-cyclodextrin (βCyD)-based carriers. The drug was incorporated in a molecular state avoiding crystallization even for long-term storage and obtaining a tenfold increased solubility up to 25mM. The binding of ETH to polymeric βCyD nanoparticles (pβCyD NPs) was investigated in neutral aqueous medium by means of solubility phase diagrams, circular dichroism (CD) and UV-vis absorption and compared with the corresponding βCyD monomer. The binding constants and the absolute CD spectra of the drug complexes were determined by global analysis of multiwavelength data from spectroscopic titrations. The spectroscopic and photophysical properties of the complexes evidenced an alcohol-like environment for ETH included in the cavity. Additionally, ETH was found to be located not only in βCyD cavities, but also in confined microdomains inside the crosslinked NPs. This double modality of complexation together with a slightly higher binding constant makes the utilization of pβCyD NPs preferable over the monomeric βCyDs. In order to pave the way to future in vitro experiments, fluorescein labeled pβCyDs were synthesized. Interestingly the FITC labeling did not hamper the encapsulation of ETH and the drug improved the fluorescent signal of FITC molecules. The βCyD-based carriers appeared as versatile "green" systems for efficient incorporation and future delivery of ETH., (Copyright © 2017 Elsevier B.V. All rights reserved.)