Preparation of a beta-Cyclodextrin Supramolecular Nanoparticle as a Drug Delivery System The design, preparation and properties.

摘要

Nanogel is a type of nano material that contains an interior gel network, and can swell to a good degree by absorbing water. It is of high interest to develop new types of nanogel for drug delivery and applications as a biomaterial. However, to be suitable for this purpose, a nanogel material should satisfy a few critical standards. Ideally, the material should have a homogeneous shape and a size less than 100 nm, and should be able to maintain such morphology upon drying and storage. It is also important that it has a relatively hydrophobic interior with good affinity to hydrophobic drugs for encapsulation. Meanwhile, a hydrophilic shell is necessary for solubility in aqueous physiological solutions. The material itself should be nontoxic, biocon patible, and biodegradable. Although some of the nanogel systems reported in the literature can fulfill some of the standards, only a few of the materials are in the clinical trial stage. An important reason is because of the complication of the preparation process.;In consideration of the above factors we designed and prepared a new pegylated beta-cyclodextrin (beta-CD) nanogel with application of the philosophies of "biomimetic" and "green chemistry". The nanogel contains only two biocompatible and biodegradable components, namely, a natural oligosaccharide, beta-cyclodextrin and a polymer widely used in biomaterials, poly (ethylene glycol). We were able to prepare the nanogel via one pot "click chemistry" in an aqueous solution at room temperature, and the process avoided initiators, organic solvents and emulsifiers. This nanogel made via the "click chemistry" process shows suitable properties to be used as a drug delivery vehicle. NMR, IR, and MALDI-TOF confirmed the formation of the covalent cross-link in the nanogel. Morphology studies by SEM and TEM indicate that the nanogel holds a relatively homogenous near-round shape, and has an average size of 87 nm. The material also maintained the morphology after drying and storage for months.;Curcumin, a hydrophobic natural compound that is believed to have many bioactivities and is not soluble in aqueous solution, was encapsulated in the nanogel with a ratio of 40 % (wt/wt) curcumin/ nanogel. The resulting product, namely curgel, can be readily dispersed in water to form a homogenous solution with an isotonic concentration at 1.4 % (wt/wt) curcumin/ water. The encapsulation was confirmed by confocal microscopy, UV-Vis and fluorescent spectrometry. The curgel was found to have the same morphology as the nanogel in shape and size. On the other hand, after drying, the curgel swells as a hydrogel when immersed in water. It can maintain the gel-like morphology and swell to 26 times its original size before being dispersed in water. This can be an interesting feature for long-term controlled release of the drug and in wound dressing.;Furthermore, the beta-CD nanogel undergoes self-assembly to form a round sphere with a size less than 100 microm. This feature makes it possible to potentially apply the beta-CD nanogel in other biological applications such as tissue engineering.