Building respirable powder architectures: utilizing polysaccharides for precise control of particle morphology for enhanced pulmonary drug delivery.

INTRODUCTION: Dry powder inhaler (DPI) formulations are gaining attention as universal formulations with applications in a diverse range of drug formulations. The practical application of DPIs to pulmonary drugs requires enhancing their delivery efficiency to the target sites for various treatment modalities. Previous reviews have not explored the relation between particle morphology and delivery to different pulmonary regions. This review introduces new approaches to improve targeted DPI delivery using novel particle design such as supraparticles and metal-organic frameworks based on cyclodextrin. AREAS COVERED: This review focuses on the design of DPI formulations using polysaccharides, promising excipients not yet approved by regulatory agencies. These excipients can be used to design various particle morphologies by controlling their physicochemical properties and manufacturing methods. EXPERT OPINION: Challenges associated with DPI formulations include poor access to the lungs and low delivery efficiency to target sites in the lung. The restricted applicability of typical excipients contributes to their limited use. However, new formulations based on polysaccharides are expected to establish a technological foundation for the development of DPIs capable of delivering modalities specific to different lung target sites, thereby enhancing drug delivery.

ß-Cyclodextrin-based nanoassemblies for the treatment of atherosclerosis.

Atherosclerosis, a chronic and progressive condition characterized by the accumulation of inflammatory cells and lipids within artery walls, remains a leading cause of cardiovascular diseases globally. Despite considerable advancements in drug therapeutic strategies aimed at managing atherosclerosis, more effective treatment options for atherosclerosis are still warranted. In this pursuit, the emergence of ß-cyclodextrin (ß-CD) as a promising therapeutic agent offers a novel therapeutic approach to drug delivery targeting atherosclerosis. The hydrophobic cavity of ß-CD facilitates its role as a carrier, enabling the encapsulation and delivery of various therapeutic compounds to affected sites within the vasculature. Notably, ß-CD-based nanoassemblies possess the ability to reduce cholesterol levels, mitigate inflammation, solubilize hydrophobic drugs and deliver drugs to affected tissues, making these nanocomponents promising candidates for atherosclerosis management. This review focuses on three major classes of ß-CD-based nanoassemblies, including ß-CD derivatives-based, ß-CD/polymer conjugates-based and polymer ß-CD-based nanoassemblies, highlighting a variety of formulations and assembly methods to improve drug delivery and therapeutic efficacy. These ß-CD-based nanoassemblies exhibit a variety of therapeutic mechanisms for atherosclerosis and offer systematic strategies for overcoming barriers to drug delivery. Finally, we discuss the present obstacles and potential opportunities in the development and application of ß-CD-based nanoassemblies as novel therapeutics for managing atherosclerosis and addressing cardiovascular diseases.

Research progress of fluorescent composites based on cyclodextrins: Preparation strategies, fluorescence properties and applications in sensing and bioimaging.

Fluorescence analysis has been regarded as one of the commonly used analytical methods because of its advantages of simple operation, fast response, low cost and high sensitivity. So far, various fluorescent probes, with noble metal nanoclusters, quantum dots, organic dyes and metal organic frameworks as representatives, have been widely reported. However, single fluorescent probe often suffers from some deficiencies, such as low quantum yield, poor chemical stability, low water solubility and toxicity. To overcome these disadvantages, the introduction of cyclodextrins into fluorescent probes has become a fascinating approach. This review (with 218 references) systematically covers the research progress of fluorescent composites based on cyclodextrins in recent years. Preparation strategies, fluorescence properties, response mechanisms and applications in sensing (ions, organic pollutants, bio-related molecules, temperature, pH) and bioimaging of fluorescent composites based on cyclodextrins are summarized in detail. Finally, the current challenges and future perspectives of these composites in relative research fields are discussed.

ZIF-8-wrapped AgNPs modified with ß-cyclodextrin for sensitive detection of thiacloprid and imidacloprid by SERS technology.

The high efficient surface-enhanced Raman scatterring (SERS) methods to detect thiacloprid and imidacloprid were established using ZIF-8-wrapped Ag nanoparticles (AgNPs) modified with ß-cyclodextrin (ß-CD). The substrate of ZIF-8/ß-CD@AgNPs was characterized by ultraviolet visible spectra (UV-vis), thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). The interaction between the substrate and thiacloprid/imidacloprid was also explored. The optimum measurement conditions were obtained by response surface model based on single-factor experiments. Enhancement factors (EFs) of thiacloprid and imidacloprid were respectively 2.29 × 106 and 2.60 × 106. A good linearity between the scattering intensity and the concentration of thiacloprid/imidacloprid within 3-1000 nmol L-1/6-400 nmol L-1 was established. The interference experiments indicated that the methods had good selectivity. The SERS methods were successfully applied to detect thiacloprid and imidacloprid in several vegetables samples. The recoveries ranged from 95.5 % to 105 % (n = 5). The detection limits (LODs) (S/N = 3) for thiacloprid and imidacloprid were 1.50 and 0.83 nmol L-1, respectively.

Porous ß-cyclodextrin polymers for rapid and efficient removal of organic micropollutants from water: The role of sulfonation and porosity on adsorption performance.

Removal of organic micropollutants (OMPs) from water, especially hydrophilic and ionized ones, is challenging for water remediation. Herein, porous ß-cyclodextrin polymers (PCPs) with tailored functionalization were prepared based on molecular expansion strategy and sulfonation. Partially benzylated ß-cyclodextrin was knotted by external crosslinker to form PCP1, and knotting PCP1 by expansion molecule generated PCP2. PCP1 and PCP2 were sulfonated to achieve PCP1-SO3H and PCP2-SO3H. Based on systematical adsorption evaluation toward multiple categories of OMPs, it was found that the introduced strong polar -SO3H group could bring strong hydrogen bonding and electrostatic interactions. PCP2 showed the highest surface (998.97 m2/g) displayed more excellent adsorption performance toward neutral and anionic OMPs, and the adsorption mechanism for this property of PCP2 was dominated by hydrophobic interactions. In addition, the PCP1-SO3H with the lowest surface area (39.75 m2/g) rather than PCP2-SO3H with higher surface (519.28 m2/g) exhibited more superior adsorption towards hydrophilic and cationic OMPs, benefiting by hydrogen bonding and electrostatic interactions as well as appropriate porosity. These results not only confirmed the performance enhancement of PCPs through the integration of novel preparation strategy, but also provided fundamental guidance for PCPs design for water remediation.

Preparation and study of a capillary electrochromatographic column prepared by conjugating ß-CD COFs and gold-poly glycidyl methacrylate nanoparticles.

A new enantioselective open-tubular capillary electrochromatography (OT-CEC) was developed employing ß-cyclodextrin covalent organic frameworks (ß-CD COFs) conjugated gold-poly glycidyl methacrylate nanoparticles (Au-PGMA NPs) as a stationary phase. The resulting coating layer on the inner wall of the fabricated capillary column was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS), and electroosmotic flow (EOF) experiments. The performance of the fabricated capillary column was evaluated by CEC using enantiomers of seven model analytes, including two proton pump inhibitors (PPIs, omeprazole and tenatoprazole), three amino acids (AAs, tyrosine, phenylalanine, and tryptophan), and two fluoroquinolones (FQs, gatifloxacin and sparfloxacin). The influences of coating time, buffer concentration, buffer pH, and applied voltage on enantioseparation were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of seven analytes were fully resolved within 10 min with high resolutions of 3.03 to 5.25. The inter- to intra-day and column-to-column repeatabilities of the fabricated capillary column were lower than 4.26% RSD. Furthermore, molecular docking studies were performed based on the chiral fabricated column and as ligand isomers of analytes using Auto Dock Tools. The binding energies and interactions acquired from docking results of analytes supported the experimental data.

The development of an innovative method to improve the dissolution performance of rivaroxaban.

Recent advancements in the formulation of solid dosage forms involving active ingredient-cyclodextrin complexes have garnered considerable attention in pharmaceutical research. While previous studies predominantly focused on incorporating these complexes into solid states, issues regarding incomplete inclusion prompted the exploration of novel methods. In this study, we aimed to develop an innovative approach to integrate liquid-state drug-cyclodextrin inclusion complexes into solid dosage forms. Our investigation centered on rivaroxaban, a hydrophobic compound practically insoluble in water, included in hydroxypropyl-ß-cyclodextrin at a 1:1 M ratio, and maintained in a liquid state. To enhance viscosity, hydroxypropyl-cellulose (2 % w/w) was introduced, and the resulting dispersion was sprayed onto the surface of cellulose pellets (CELLETS®780) using a Caleva Mini Coater. The process parameters were meticulously controlled, with atomization air pressure set at 1.1 atm and a fluidizing airflow maintained at 35-45 m3/h. Characterization of the coated cellets, alongside raw materials, was conducted using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses. Physicochemical evaluations affirmed the successful incorporation of rivaroxaban into hydroxypropyl-ß-cyclodextrin, with the final cellets demonstrating excellent flowability, compressibility, and adequate hardness. Quantitative analysis via the HPLC-DAD method confirmed a drug loading of 10 mg rivaroxaban/750 mg coated cellets. In vitro dissolution studies were performed in two distinct media: 0.022 M sodium acetate buffer pH 4.5 with 0.2 % sodium dodecyl sulfate (mirroring compendial conditions for 10 mg rivaroxaban tablets), and 0.05 M phosphate buffer pH 6.8 without surfactants, compared to reference capsules and conventional tablet formulations. The experimental capsules exhibited similar release profiles to the commercial product, Xarelto® 10 mg, with enhanced dissolution rates observed within the initial 10 min. This research presents a significant advancement in the development of solid dosage forms incorporating liquid-state drug-cyclodextrin inclusion complexes, offering a promising avenue for improving drug delivery and bioavailability.

An Artificial Light-Harvesting System based on Supramolecular AIEgen Assembly.

Photosynthesis is a complex multi-step process in which light collection is the initial step of photosynthesis and plays an important role in the efficiency of solar energy utilization. In order to improve the utilization of sunlight, researchers have developed a variety of artificial light-harvesting system to simulate photosynthesis in nature. Here, we report a supramolecular self-assembly artificial light-harvesting system in aqueous solution.  We modified ß-CD with the donor molecule naphthalimide and adamantane with the tetraphenylethylene molecule which has aggregation-induced emission effects (AIE). By using fluorescent molecules with AIE, the self-quenching effect caused by aggregation in aqueous solution can be effectively avoided. Due to the host-guest interaction of ß-CD and adamantane, nanoparticles with stable structure and uniform size can be spontaneously assembled in water. Because of the close distance and strong spectral overlap between naphthalimide and tetraphenylethylene, Förster resonance energy transfer (FRET) was realized, and artificial light-harvesting system was successfully constructed in aqueous solution. The light-harvesting system has a high energy transfer efficiency (ΦET). Therefore, this study provides a new strategy for constructing artificial light-harvesting system.

Adsorption performance and mechanism of pectin modified with ß-cyclodextrin for Zn2+ and Cu2.

Removing heavy metals from aqueous solutions has drawn more and more attentions these years because of their serious global health challenge to human society. To develop an adsorbent with green, stable and high-efficiency for adsorption of heavy metals, pectin ß-cyclodextrin composite was successfully prepared and used for Zn2+ and Cu2+ adsorption for the first time. Various variables that influence the adsorption performance were explored, and the optimal adsorption conditions were determined. According to the pseudo-second-order kinetic model, the adsorption process of Zn2+ and Cu2+ by the adsorbent was mainly chemical adsorption. The adsorbent adsorption process was an exothermic and non-spontaneous process. According to the Langmuir isotherm model, the maximum adsorption capacity was 12.51 ± 0.33 and 24.98 ± 0.23 mg/g for Zn2+ and Cu2+, respectively. The FTIR, EDX and XPS results revealed that the main mechanisms of removing pollutants by adsorbent were ion exchange and coordination. In addition, electrostatic attraction and chelation were present in the adsorption process. After five adsorption desorption cycles, the pectin ß-cyclodextrin composite adsorbent still exhibited adsorption and regeneration capabilities. This study provides a low-cost, effective and simple method for preparation of modified pectin, which has excellent application potential in the removal of heavy metal ions from wastewater.

Fluorogenic Monitoring of α-Amylase in Human Urine for Straightforward Diagnosis of Pancreatic Diseases.

In this study, we developed a sensitive method for monitoring α-amylase using a fluorogenic approach based on the host-guest complexation between an amphiphilic pyrenyl derivative (1) and γ-cyclodextrins (γ-CDs). The compound 1 self-assembles into nanofibrils in aqueous solutions. Upon the introduction of γ-CD, compound 1 forms an inclusion complex with it. This complex then participates in the formation of a 2:2 complex with another complex, leading to strong excimer fluorescence. Upon interaction with α-amylase, γ-CD undergoes hydrolysis, leading to the regeneration of nanofibrils, which is accompanied by a decrease in excimer fluorescence and an increase in monomeric fluorescence. This ratiometric fluorescence color change enables the sensitive detection of low levels of α-amylase in human urine, offering a practical approach for early screening of pancreatic-related diseases.

Cyclodextrins as a Strategy for Enhancing Solubility of Therapeutic Agents for Neglected Tropical Diseases: A Systematic Review.

BACKGROUND: Neglected Tropical Diseases (NTD) are chronic infectious conditions that primarily affect marginalized populations. The chemotherapeutic arsenal available for treating NTD is limited and outdated, which poses a challenge in controlling and eradicating these diseases. This is exacerbated by the pharmaceutical industry's lack of interest in funding the development of new therapeutic alternatives. In addition, a considerable number of drugs used in NTD therapy have low aqueous solubility. To address this issue, solubility enhancement strategies, such as the use of inclusion complexes with cyclodextrins (CD) can be employed. OBJECTIVE: Therefore, this systematic review aims to present the application of CD in complexing with drugs and chemotherapeutic compounds used in the therapy of some of the most prevalent NTD worldwide and how these complexes can enhance the treatment of these diseases. METHODS: Two bibliographic databases, Science Direct and PubMed, were used to conduct the search. The selection of studies and the writing of this systematic review followed the criteria outlined by the PRISMA guidelines. RESULTS: From a total of 978 articles, 23 were selected after applying the exclusion criteria. All the studies selected were consistent with the use of CD as a strategy to increase the solubility of therapeutic agents used in NTD. CONCLUSION: The results indicate that CD can enhance the solubility of chemotherapeutic agents for the treatment of Neglected Tropical Diseases (NTD). This review presents data that clearly highlights the potential use of CD in the development of new treatments for neglected tropical diseases. It can assist in the formulation of future treatments that are more effective and safer.

Preparation, Characterization, and Oral Bioavailability of Solid Dispersions of Cryptosporidium parvum Alternative Oxidase Inhibitors.

The phenylpyrazole derivative 5-amino-3-[1-cyano-2-(3-phenyl-1H-pyrazol-4-yl) vinyl]-1-phenyl-1H-pyrazole-4-carbonitrile (LN002), which was screened out through high-throughput molecular docking for the AOX target, exhibits promising efficacy against Cryptosporidium. However, its poor water solubility limits its oral bioavailability and therapeutic utility. In this study, solid dispersion agents were prepared by using HP-ß-CD and Soluplus® and characterized through differential scanning calorimetry, Fourier transform infrared, powder X-ray diffraction, and scanning electron microscopy. Physical and chemical characterization showed that the crystal morphology of LN002 transformed into an amorphous state, thus forming a solid dispersion of LN002. The solid dispersion prepared with an LN002/HP-ß-CD/Soluplus® mass ratio of 1:3:9 (w/w/w) exhibited significantly increased solubility and cumulative dissolution. Meanwhile, LN002 SDs showed good preservation stability under accelerated conditions of 25 °C and 75% relative humidity. The complexation of LN002 with HP-ß-CD and Soluplus® significantly improved water solubility, pharmacological properties, absorption, and bioavailability.

Facile Preparation of Tough, Puncture-Resistant Antibacterial Polyrotaxane Hydrogel.

Slide-ring hydrogels containing polyrotaxane structures have been widely developed, but current methods are more complex, in which modified cyclodextrins, capped polyrotaxanes, and multistep reactions are often needed. Here, a simple one-pot method dissolving the pseudopolyrotaxane (pPRX) in a mixture of acrylamide and boric acid to form a slide-ring hydrogel by UV light is used to construct a tough, puncture-resistant antibacterial polyrotaxane hydrogel. As a new dynamic ring cross-linking agent, boric acid effectively improves the mechanical properties of the hydrogel and involves the hydrogel with fracture toughness. The polyrotaxane hydrogel can withstand 1 MPa compression stress and maintain the morphology integrity, showing 197.5 mJ puncture energy under a sharp steel needle puncture. Meanwhile, its significant antibacterial properties endow the hydrogel with potential applications in the biomedical field.

Evaluation of functional transbilayer coupling in live cells by controlled lipid exchange and imaging fluorescence correlation spectroscopy.

Biophysical coupling between the inner and outer leaflets, known as inter-leaflet or transbilayer coupling, is a fundamental organizational principle in the plasma membranes of live mammalian cells. Lipid-based interactions between the two leaflets are proposed to be a primary mechanism underlying transbilayer coupling. However, there are only a few experimental evidence supporting the existence of such interactions in live cells. This is seemingly due to the lack of experimental strategies to perturb the lipid composition in one leaflet and quantitative techniques to evaluate the biophysical properties of the opposite leaflet. The existing strategies often dependent on immobilization and clustering a component in one of the leaflets and technically demanding biophysical tools to evaluate the effects on the opposing leaflet. In the recent years, the London group developed a simple but elegant method, namely methyl-alpha-cyclodextrin catalyzed lipid exchange (LEX), to efficiently exchange outer leaflet lipids with an exogenous lipid of choice. Here, we adopted this method to perturb outer leaflet lipid composition. The corresponding changes in the inner leaflet is evaluated by comparing the diffusion of lipid probes localized in this leaflet in unperturbed and perturbed conditions. We employed highly multiplexed imaging fluorescence correlation spectroscopy (ImFCS), realized in a commercially available or home-built total internal reflection fluorescence microsocope equipped with a fast and sensitive camera, to determine diffusion coefficient of the lipid probes. Using the combination of LEX and ImFCS, we directly demonstrate lipid-based transbilayer coupling that does not require immobilization of membrane components in live mast cells in resting conditions. Overall, we present a relatively straightforward experimental strategy to evaluate transbilayer coupling quantitively in live cells.

MαCD-based plasma membrane outer leaflet lipid exchange in mammalian cells to study insulin receptor activity.

Signaling receptors on the plasma membrane, such as insulin receptor, can have their activity modulated to some extent by their surrounding lipids. Studying the contribution of membrane lipid properties such as presence of ordered lipid domains or bilayer thickness on the activity of receptors has been a challenging objective in living cells. Using methyl-alpha cyclodextrin-mediated lipid exchange, we are able to alter the lipids of the outer leaflet plasma membrane of mammalian cells to investigate the effect of the properties of the exchanged lipid upon receptor function in live cells. In this article, we describe the technique of lipid exchange in detail and how it can be applied to better understand lipid-mediated regulation of insulin receptor activity in cells.

Efficient PFAS removal from contaminated soils through combined washing and adsorption in soil effluents.

This study investigates soil washing as a viable strategy to remove poly- and perfluoroalkyl substances (PFAS) from contaminated soils using various washing agents including water, methanol, ethanol, and cyclodextrin ((2-Hydroxypropyl)-ß-cyclodextrin HPCD)). Water was less effective (removing only 30 % of PFAS), especially for long-chain hydrophobic PFAS. Methanol (50 % v/v) or HPCD (10 mg g-1 soil) achieved > 95 % PFAS removal regardless of PFAS type, soil size fraction (0-400 µm or 400-800 µm), or experimental setups (batch or column, at liquid/solid (L/S) = 1). Column optimization studies revealed improved efficiency at L/S = 10 with diluted washing solutions, where HPCD exhibited rapid PFAS mobilization even at lower concentrations (1 mg mL-1). We then applied a first-order decay model to effectively predict PFAS breakthrough curves and mobilization within soil columns. Subsequent treatment of wash effluents by activated carbon and biochar effectively reduced PFAS concentrations below detection limits. The performance of both soil washing and subsequent adsorption was found to depend strongly on the specific characteristics of PFAS compounds. These findings highlight the significant potential of methanol and HPCD in soil washing and the effectiveness of integrated soil washing and adsorption for optimizing PFAS removal.

Fabrication of a salivary amylase electrochemical sensor based on surface confined MWCNTs/ß-cyclodextrin/starch architect for dental caries in clinical samples.

Salivary α-amylase (α-ALS) has drawn attention as a possible bioindicator for dental caries. Herein, combining the synergistic properties of multi-walled carbon nanotubes (MWCNTs), ß-cyclodextrin (ß-CD) and starch, an electrochemical sensor is constructed employing ferrocene (FCN) as an electrochemical indicator to oversee the progression of the enzymatic catalysis of α-ALS. The method involves a two-step chemical reaction sequence on a screen-printed carbon electrode (SPCE). X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscope (FE-SEM), and Dynamic light scattering (DLS) were used to characterize the synthesized material, while Static water Contact angle measurements, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) were performed to monitor each step of sensor fabrication. The electrochemical sensor permitted to detect α-ALS within the linear range of 0.5-280 U mL-1, revealing detection (LOD), and quantification (LOQ) values of 0.041 U mL-1, and 0.159 U mL-1, respectively. Remarkably, the sensor demonstrated exceptional specificity and selectivity, effectively discriminating against other interfering substances in saliva. Validation of the method involved analyzing α-ALS levels in artificial saliva with an accuracy range of 97 % to 103 %, as well as in real clinical saliva samples across various age groups.

Cyclodextrin-modified PVDF membranes with improved anti-fouling performance.

The design of hydrophilic polyvinylidene fluoride (PVDF) membranes with anti-fouling properties has been explored for decades. Surface modification and blending are typical strategies to tailor the hydrophilicity of PVDF membranes. Herein, cyclodextrin was used to improve the antifouling performance of PVDF membranes. Cyclodextrin-modified PVDF membranes were prepared by coupling PVDF amination (blending with branched polyethyleneimine) and activated cyclodextrin grafting. The blending of PEI in the PVDF casting solution preliminarily aminated the PVDF, resulting in PEI-crosslinked/grafted PVDF membranes after phase inversion. Aldehydes groups on cyclodextrin, introduced by oxidation, endow cyclodextrin to be grafted on the aminated PVDF membrane by the formation of imines. Borch reduction performed on the activated cyclodextrin-grafted PVDF membrane converted the imine bonds to secondary amines, ensuring the membrane stability. The resulting membranes possess excellent antifouling performance, with a lower protein adsorption capacity (5.7 µg/cm2, indicated by Bovine Serum Albumin (BSA)), and a higher water flux recovery rate (FRR = 96%). The proposed method provides a facial strategy to prepare anti-fouling PVDF membranes.

Host-Guest Complexes of Flavanone and 4'-Chloroflavanone with Naturals and Modified Cyclodextrin: A Calorimetric and Spectroscopy Investigations.

The aim of the research was to investigate and compare the interaction between flavanones (flavanone, 4-chloro-flavanone) with potential anticancer activity and selected cyclodextrins. Measurements were made using calorimetric (ITC, DSC) and spectrophotometric (UV-Vis spectroscopy, FT-IR, 1H NMR) methods. The increase in the solubility in aqueous medium caused by the complexation process was determined by the Higuchi-Connors method. As a result of the study, the stoichiometry and thermodynamics of the complexation reaction were determined. The formation of stable inclusion complexes at a 1:1 M ratio between flavanone and 4-chloroflavanone and the cyclodextrins selected for research was also confirmed.

A Review of Machine Learning and QSAR/QSPR Predictions for Complexes of Organic Molecules with Cyclodextrins.

Cyclodextrins are macrocyclic rings composed of glucose residues. Due to their remarkable structural properties, they can form host-guest inclusion complexes, which is why they are frequently used in the pharmaceutical, cosmetic, and food industries, as well as in environmental and analytical chemistry. This review presents the reports from 2011 to 2023 on the quantitative structure-activity/property relationship (QSAR/QSPR) approach, which is primarily employed to predict the thermodynamic stability of inclusion complexes. This article extensively discusses the significant developments related to the size of available experimental data, the available sets of descriptors, and the machine learning (ML) algorithms used, such as support vector machines, random forests, artificial neural networks, and gradient boosting. As QSAR/QPR analysis only requires molecular structures of guests and experimental values of stability constants, this approach may be particularly useful for predicting these values for complexes with randomly substituted cyclodextrins, as well as for estimating their dependence on pH. This work proposes solutions on how to effectively use this knowledge, which is especially important for researchers who will deal with this topic in the future. This review also presents other applications of ML in relation to CD complexes, including the prediction of physicochemical properties of CD complexes, the development of analytical methods based on complexation with CDs, and the optimisation of experimental conditions for the preparation of the complexes.