β-Cyclodextrin (β-CD) has attracted widespread attention due to its good biocompatibility and biodegradability. Under the action of cyclodextrin glycosyltransferase produced by Bacillus, cyclodextrin is a series of cyclic cyclodextrins containing 6 to 12 D-glucopyranoside units connected through 1,4-glycosidic bonds produced by amylose. The general term for oligosaccharides includes three types of cyclodextrins: α-, β-, and γ-. According to the results of X-ray crystal diffraction, infrared spectrum and nuclear magnetic resonance spectrum analysis, it was determined that each D(+)-glucopyranose constituting the cyclodextrin molecule is in the chair conformation. Each glucose unit is combined with a 1,4-glycosidic bond to form a ring. Because the glycosidic bonds connecting the glucose units cannot rotate freely, cyclodextrin is not a cylindrical molecule but a slightly tapered ring. The white powdery β-cyclodextrin structure contains many hydroxyl groups, making it highly polar. Its solubility in ethyl acetate, ether, ethanol, and methanol is very small, and it is easily soluble in highly polar solvents such as dimethyl sulfoxide, N, N-dimethylformamide, and pyridine. β-Cyclodextrin has many advantages: (1) It has good emulsification and dispersion properties; (2) It can reduce volatilization, reduce toxicity, and improve solubility; (3) It is also excellent in moisture-proofing, moisturizing, and extending the efficacy of preparations. Large closed hydrogen bonding bands are formed between adjacent hydroxyl groups in the β-cyclodextrin molecule. Therefore, although there are free hydroxyl groups, the solubility in water is very low compared with the other two cyclodextrins. β-Cyclodextrin can exist stably in alkaline solutions. Under acidic conditions, part of β-cyclodextrin will be hydrolyzed into a series of acyclic maltose and glucose series. β-Cyclodextrin does not have a clear melting point, but it begins to decompose when the temperature rises to 200°C. β-cyclodextrin can be extracted from natural polymer materials. It has many advantages, such as wide sources, low toxicity, low production cost, and biodegradability. And because of its special structure of hydrophilic on the outside and hydrophobic on the inside, it can be modified, in order to obtain better characteristics and greatly improve the application effect. As a clean and green carrier material, β-cyclodextrin has the advantages of being non-toxic, odorless and harmless to the human body, and is widely used in medicine, food, water treatment and other fields.
Figure 1. Schematic chemical structure and conformation of 2-hydroxypropyl β-cyclodextrin (HP-β-CD).(Stolzke T, et al. 2022)
Since the outer rim (Rim) of cyclodextrin is hydrophilic and the inner cavity (Cavity) is hydrophobic, it can provide a hydrophobic binding site like an enzyme and serve as a host to envelop various appropriate guests, such as Organic molecules, inorganic ions, gas molecules, etc. The hydrophobic inner cavity and hydrophilic outer cavity allow it to form inclusion complexes and molecular assembly systems with many organic and inorganic molecules based on van der Waals forces, hydrophobic interactions, and matching between host and guest molecules, making it a popular choice for chemical and chemical engineering research. This selective enveloping effect is commonly known as molecular recognition, and the result is the formation of a host-guest complex. Cyclodextrin is the ideal enzyme-like host molecule found so far, and it itself has the characteristics of an enzyme model. For this reason, cyclodextrins have received great attention and are widely used in the fields of catalysis, separation, food and medicine. Due to the solubility and inclusion ability of cyclodextrin in water, changing the physical and chemical properties of cyclodextrin has become one of the important purposes of chemical modification of cyclodextrin.
With the continuous development of nanomaterials, research on targeted controlled release of drugs has received widespread attention. Emerging β-cyclodextrin nanoparticles have good biocompatibility and degradability. β-cyclodextrin is used to react with small molecular substances and then grafted with magnetic particles, etc., which can be widely used in the field of drug delivery. Composite materials composed of β-cyclodextrin, magnetic Fe3O4, and other small molecule substances can be used in areas such as targeted therapy, drug delivery, and medical testing. Some researchers grafted carboxyl-modified β-cyclodextrin onto the surface of aminated Fe3O4-loaded polyester fabric, and included menthol inside the β-cyclodextrin cavity to characterize its drug-loading performance. It was found that there was no obvious change in the appearance of the polyester, but there were obvious cracks between the polyester fibers and some small particles appeared. The study found that the compound did not change before and after inclusion in the system, the particles showed weak magnetism, and the inclusion effect was very good, and the drug could be released slowly. Others have prepared pH-sensitive composite micelles of chitosan grafted with β-cyclodextrin (CS-g-CD) and benzimidazole-terminated poly(ε-caprolactone) (BM-PCL), using to control drug release. The composite micelle has a core-shell structure. The core is formed by BM-PCL and CD through host-guest interaction, and the shell is formed by chitosan chains. Doxorubicin (DOX) is a model anticancer drug that is efficiently loaded into complex micelles through hydrophobic interactions. Experimental results show that the DOX encapsulation rate reaches 75%. The release experiments of DOX in micelles show that the release is inhibited in neutral pH solutions and accelerated in acidic solutions and high temperatures. Such pH-sensitive micelles may have potential applications in the delivery of anticancer drugs using smart nanocarriers.
Alternate Names:
β-CD
Schardinger β-dextrin
References:
1. Stolzke T, et al. Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations. Molecules. 2022, 27(16):5094.
Sulfobutylether-β-cyclodextrin: A functional biopolymer for drug delivery applications
Carbohydr Polym
Authors: Pardeshi CV, Kothawade RV, Markad AR, Pardeshi SR, Kulkarni AD, Chaudhari PJ, Longhi MR, Dhas N, Naik JB, Surana SJ, García MC.
Abstract
Sulfobutylether β-cyclodextrin (SBE-β-CD) is a polyanionic cyclic oligosaccharide that contains glucopyranose units forming a torus ring-like structure. SBE-β-CD is gifted with many favorable properties viz. relatively high solubility (>50 folds compared to β-CD), improved stability, and biocompatibility that praised SBE-β-CD as a smart polymer for drug delivery applications. Commercially, SBE-β-CD is popular by its brand name Captisol®. The present review discusses the structure, properties, and preparation methods of SBE-β-CD-based inclusion complexes (ICs). Furthermore, we discuss here the preparation and applications of SBE-β-CD ICs-based nanoparticulate drug delivery systems, which combines the merits of both, ICs (enhanced solubility) and nanoparticles (NPs, targeted therapy). Patents on and FDA-approved Captisol®-enabled products are tabulated in the benefit of readers. The toxicological aspects and current clinical status of SBE-β-CD or SBE-β-CD-based products are briefly explained in the present review. In our opinion, the present review would be a pathfinder to allow dissemination of information on SBE-β-CD.
Drug delivery based on chitosan, β-cyclodextrin and sodium carboxymethyl cellulose as well as nanocarriers for advanced leukemia treatment
Biomed Pharmacother
Authors: Hosseini M, Amiri M, Ghanbari M, Mahdi MA, Abdulsahib WK, Salavati-Niasari M.
Abstract
Medicine/nanotechnology as a new and applicable technique according to drug delivery systems has gained great consideration for cancer treatment. Polysaccharides including, cellulose, β-cyclodextrin and sodium carboxymethyl cellulose and chitosan as natural bio-materials, are appropriate candidates for designing and formulations of these nanosystems because of the exceptional advantages such as bio-compatibility, bio-degradability, non-toxicity, and gelling characteristics. An intelligent drug delivery platform based on these hybrids nowadays is developed, which can be used for dual-responsive dual-drug delivery. Nanotechnology accompany with biological molecules has been carefully considered to decrease the drawbacks of conventional cancer treatments. Consequently, this review is intended to state and investigate on the latest development on the combination treatment of platforms based on the hybrids of anticancer drugs/nanoparticles/Polysaccharides in the fields of biomedical therapeutics and cancer therapy owing to the bio-compatibility, great surface area, good chemical and mechanical features, the challenges and future perspectives are reported as well.
Multifunctional β-Cyclodextrin-Poly(ethylene glycol)-Cholesterol Nanomicelle for Anticancer Drug Delivery
ACS Appl Bio Mater
Authors: Yang D, Yang S, Mu M, Liu X, Zhao L, Xu Z, Mu C, Li D, Ge L.
Abstract
Nanoparticle drug delivery systems have drawn considerable attention worldwide due to their unique characteristics and advantages in anticancer drug delivery. Herein, the curcumin (Cur) loaded nanomicelles with two-stage drug release behavior were developed. β-Cyclodextrin (β-CD) and cholesterol were conjugated onto both ends of the poly(ethylene glycol) (PEG) chain to obtain an amphiphilic β-CD-PEG-Chol. The Cur was loaded into the cavities of β-CD and nanomicelle when the β-CD-PEG-Chol self-assembled to the Cur@β-CD-PEG-Chol nanomicelles (Cur@CPC NMs). These Cur@CPC NMs are spherical particles with a particle size of 120.9 nm. The Cur drug loading capacity of Cur@CPC NMs are 61.6 ± 6.9 mg/g. The release behavior of Cur from Cur@CPC NMs conformed to a two-stage mode of "burst-release followed by sustained-release". The prepared Cur@CPC NMs possess high storage stability and excellent hemocompatibility. Moreover, these Cur@CPC NMs exhibit satisfactory antioxidant activity and anticancer activity, resulting in significant reduction in intracellular H2O2-induced ROS and a nearly 50% lethality rate of HepG-2 cells. Meanwhile, the Cur@CPC NMs show good anti-inflammatory activity, by which the secretion of inflammatory factors of IL-6 and TNF-α are inhibited. Overall, the developed Cur@CPC NMs show application prospects in anticancer drug delivery systems.
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