Synthesis and Characterization of the Inclusion Complex of Dicationic Ionic Liquid and β-Cyclodextrin

The supramolecular structure of the inclusion complex of β-cyclodextrin (β-CD) with 1,1′,2,2′-tetramethyl-3,3′-(p-phenylenedimethylene) diimidazolium dibromide (TetraPhimBr), a dicationic ionic liquid, has been investigated. The inclusion complex with 1:1 molar ratio was prepared by a kneading method. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) analysis, 1H NMR and thermogravimetric analysis (TGA) confirmed the formation of the inclusion complex. The results showed that the host-guest system is a fine crystalline powder. The decomposition temperature of the inclusion complex is lower than that of its parent molecules, TetraPhimBr and β-CD individually

Synthesis of β‐Cyclodextrin Containing Copolymer via “Click” Chemistry and Its Self‐Assembly in the Presence of Guest Compounds

We report the synthesis of a hydrophilic copolymer with one polyethylene glycol (PEG) block and one β‐cyclodextrin (β‐CD) containing block by a “click” reaction between azido‐substituted β‐CD and propargyl flanking copolymer. 1 H NMR study suggested a highly efficient conjugation of β‐CD units by this approach. The obtained copolymer was used as a host macromolecule to construct assemblies in the presence of hydrophobic guests. For assemblies containing a hydrophobic polymer, their size can be simply adjusted by simply changing the content of hydrophobic component. By serving as a guest molecule, hydrophobic drugs can also be loaded accompanying the formation of nanoparticles, and the drug payload is releasable. Therefore, the copolymer synthesized herein can be employed as a carrier for drug delivery. The synthesis of β‐cyclodextrin containing block copolymer via a “click” reaction is reported. The self‐assembly of this newly synthesized copolymer in the presence of guest compounds can lead to the formation of core–shell structured nanoparticles. These assemblies can be employed as novel delivery vehicles for therapeutics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91173/1/marc_201100814_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91173/2/664_ftp.pd

Cyclodextrin modulation of gallic acid in vitro antibacterial activity

The substitution of large spectrum antibiotics for natural bioactive molecules (especially polyphenolics) for the treatment of wound infections has come into prominence in the pharmaceutical industry. However, the use of such molecules depends on their stability during environmental stress and on their ability to reach the action site without losing biological properties. The application of cyclodextrins as a vehicle for polyphenolics protection has been documented and appears to enhance the properties of bioactive molecules. Therefore, the encapsulation of gallic acid, an antibacterial agent with low stability, by -cyclodextrin, (2-hydroxy) propyl--cyclodextrin and methyl--cyclodextrin, was investigated. Encapsulation by -cyclodextrin was confirmed for pH 3 and 5, with similar stability parameters. The (2-hydroxy) propyl--cyclodextrin and methyl--cyclodextrin interactions with gallic acid were only confirmed at pH 3. Among the three cyclodextrins, better gallic acid encapsulation were observed for (2-hydroxy) propyl--cyclodextrin, followed by -cyclodextrin and methyl--cyclodextrin. The effect of cyclodextrin encapsulation on the gallic acid antibacterial activity was also analysed. The antibacterial activity of the inclusion complexes was investigated here for the first time. According to the results, encapsulation of gallic acid by (2-hydroxy) propyl--cyclodextrin seems to be a viable option for the treatment of skin and soft tissue infections, since this inclusion complex has good stability and antibacterial activity.The authors are grateful for the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the Project "BioHealth-Biotechnology and Bioengineering approaches to improve health quality", Ref. NORTE-07-0124-FEDER-000027, co-funded by the "Programa Operacional Regional do Norte" (ON.2-O Novo Norte), QREN, FEDER. The authors also acknowledge the project "Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB", Ref. FCOMP-01-0124-FEDER-027462. This work is, also, funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through FCT-Foundation for Science and Technology under the project PEst-C/CTM/UI0264/2011. Additionally, the authors would like to thank the FCT for the grant for E. Pinho (SFRH/BD/62665/2009)

Self-Assembled Hydrogels Based on B-Cyclodextrin/Cholesterol Inclusion Complexes : Properties and Pharmaceutical Applications

Hydrogels, i.e. hydrophilic polymer networks that are capable of absorbing considerable quantities of water, are applied in a wide variety of biomedical and pharmaceutical applications, including soft contact lenses, drug delivery depots and tissue engineering scaffolds. Their high water content gives hydrogels a rubbery appearance, which minimizes irritation of surrounding tissue, and creates a natural environment for many encapsulated drugs (e.g. protein pharmaceuticals). In aqueous environment, hydrogels are held together by crosslinks, which are based on either covalent bonds or physical interactions between the hydrophilic polymers. The introduction of covalent bonds between the hydrophilic polymer chains requires chemical crosslinking reactions that might potentially affect the structure and biological activity of encapsulated pharmaceuticals. Furthermore, these chemical reactions often require crosslinking reagents or catalysts that are toxic towards cells. Because of these drawbacks, the use of physical crosslinks for the design of hydrogel systems is preferred. In such hydrogels the network is held together by non-permanent, reversible interactions between the polymer chains, such as ionic interactions, hydrophobic interactions, hydrogen bonds and specific biomimetic interactions. In the thesis of Frank van de Manakker, the synthesis and characterization of novel self-assembled hydrogels is described in which physical crosslinking is established by host-guest inclusion complexes between the cyclic oligosaccharide beta-cyclodextrin (betaCD) and the complementary guest molecule cholesterol. Hydrogel building blocks were prepared by end-modification of 8-arm star shaped poly(ethylene glycol) (PEG8) with either betaCD or cholesterol moieties via a hydrolytically cleavable succinyl linker. Mixing the resulting cholesterol- and betaCD-derivatized PEG8-molecules in aqueous solution led to hydrogel formation. Important gel properties, i.e. mechanical properties, gel degradation and protein release kinetics, could be tailored by a broad range of parameters, including the polymer concentration, B-?CD/cholesterol stoichiometry, PEG’s molecular weights and/or architecture, or by adding molecules that form competing inclusion complexes, e.g. adamantanecarboxylic acid and monoamino-derivatized betaCD. The physical nature of the gels did not only offer extra tools to manipulate gel properties, but also rendered the gels responsive towards external stimuli, such as temperature and mechanical stresses, which offered the opportunity to use the hydrogels as injectable, in situ gelling devices. When aqueous media (e.g. buffer and serum) were added on top of the self-assembled gels, hydrogel degradation was primarily mediated by surface erosion of dissociated PEG8 derivatives. This degradation mechanism, which is hardly observed for other hydrogel systems, also controlled protein release from the gels, which occurred at a constant rate and was nearly independent on protein size. Although at this stage, the in vivo stability of the hydrogels requires further improvement, the combination of tunable properties, high gel strengths (compared to other physically crosslinked hydrogels), the unique protein release mechanism, and easy preparation from biocompatible and well-available building blocks make these self-assembled, PEG8-based hydrogels attractive candidates for many pharmaceutical and biomedical applications, such as injectable devices for the delivery of protein pharmaceuticals