Supramolecular hydrogels formed by ß-cyclodextrin self-association and host–guest inclusion complexes

Supramolecular hydrogels are highly interesting for drug delivery and tissue engineering applications, especially those systems that display a combination of tunable properties, high mechanical strength and easy preparation from well-available and biocompatible building blocks. In the present paper, we show that the combination of free β-cyclodextrin (βCD) and 8-arm or linear cholesterol-derivatized poly(ethylene glycol) (PEG–chol) in aqueous solution resulted in the formation of almost fully elastic gels with storage moduli in the range of 10–500 kPa. X-Ray diffraction measurements demonstrated the presence of crystalline βCD domains in the hydrogel networks. Rheological experiments further proved that hydrogel formation is based on inclusion complex formation between these βCD clusters and cholesterol coupled to the terminal end of PEG. The observation that the gels were weakened by addition of the competitive βCD–guest molecule adamantanecarboxylic acid (ACA) supported the proposed gelation mechanism. The gel mechanical properties were dependent on temperature, concentration of cholesterol-derivatized PEG and/or βCD, PEG's molecular weight and its architecture. This hydrogel system can be considered as an excellent candidate for future applications in the biomedical and pharmaceutical fields

Pharmacological differences between human and guinea pig histamine H1 receptors: Asn84 (2.61) as key residue within an additional binding pocket in the H1 receptor

We tested several histamine

Effect of polymer composition on rheological and degradation properties of temperature-responsive gelling systems composed of acyl-capped PCLA-PEG-PCLA.

In this study, the ability to modulate the rheological and degradation properties of temperature-responsive gelling systems composed of acyl-capped poly(epsilon-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(epsilon-caprolactone-co-lactide) (PCLA-PEG-PCLA) triblock copolymers was investigated. Eight polymers with varying molecular weight of PCLA, caproyl/lactoyl ratio (CL/LA) and capped with either acetyl- or propionyl-groups were synthesized by ring-opening polymerization of L-lactide and epsilon-caprolactone in toluene using PEG as initiator and tin(II) 2-ethylhexanoate as catalyst, and subsequently reacted in solution with an excess of acyl chloride to yield fully acyl-capped PCLA-PEG-PCLA. The microstructure of the polymers was determined by (1)H NMR, and the thermal properties and crystallinity of the polymers in dry state and in 25 wt % aqueous systems were studied by differential scanning calorimetry and X-ray diffraction. Rheological and degradation/dissolution properties of aqueous systems composed of the polymers in 25 wt % aqueous systems were studied. (1)H NMR analysis revealed that the monomer sequence in the PCLA blocks was not fully random, resulting in relatively long CL sequences, even though transesterification was demonstrated by the enrichment with lactoyl units and the presence of PEG-OH end groups. Except the most hydrophilic polymer composed of acetyl-capped PCLA1400-PEG1500-PCLA1400 having a CL/LA molar ratio of 2.5, the polymers at 25 wt % in buffer were sols below room temperature and transformed into gels between room temperature and 37 degrees C, which makes them suitable as temperature-responsive gelling systems for drug delivery. Over a period of weeks at 37 degrees C, the systems containing polymers with long CL sequences (~8 CL) and propionyl end-groups became semicrystalline as shown by X-ray diffraction analysis. Degradation of the gels by dissolution at 37 degrees C took 100-150 days for the amorphous gels and 250-300 days for the semicrystalline gels. In conclusion, this study shows that changes in the polymer composition allow an easy but significant modulation of rheological and degradation properties

Cholesterol Depletion Using Methyl-β-cyclodextrin

Cholesterol is an essential component of mammalian cells. It is the major lipid constituent of the plasma membrane and is also abundant in most other organelle membranes. In the plasma membrane cholesterol plays critical physical roles in the maintenance of membrane fluidity and membrane permeability. It is also important for membrane trafficking, cell signalling, and lipid as well as protein sorting. Cholesterol is essential for the formation of liquid ordered domains in model membranes, which in cells are known as lipid nanodomains or lipid rafts. Cholesterol depletion is widely used to study the role of cholesterol in cellular processes and can be performed over days using inhibitors of its synthesis or acutely over minutes using chemical reagents. Acute cholesterol depletion by methyl-β-cyclodextrin (MBCD) is the most widely used method and here we describe how it should be performed to avoid the common side-effect cell death