Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

Purpose: The aim of this research was to prepare adhesive nanoparticles for the topical application of Minoxidil (MXD). Methods: Thiolated β-CDs were prepared via conjugation of cysteamine with oxidized CDs. MXD was encapsulated within thiolated and unmodified β-CDs. Nanoparticles (Thio-NP and blank NP) were prepared by ionic gelation of CDs with chitosan. Particle size and zeta potential were measured. FTIR analyses were performed for characterization of inclusion complex. Drug dissolution studies were carried out. An in vitro adhesion study over human hair was performed. An in vivo skin irritation study was performed. Ex vivo drug uptake was evaluated by using a Franz diffusion cell. Results: Thiolated β-CDs presented 1804.68 ± 25 μmol/g thiol groups and 902.34 ± 25 μmol/g disulfide bonds. Nanoparticles displayed particle sizes within a range of 231 nm to 319 nm. The zeta potential was in the range of ̶ 8.1 to + 12.0. FTIR analyses confirmed no interaction between the excipients and drug. Delayed drug release was observed from Thio-NP. Thio-NP retained over hair surfaces for a significantly longer time. Similarly, drug retention was significantly improved. Thio-NP displayed no irritation over rabbit skin. Conclusion: Owing to the above results, nanoparticles developed with MXD-loaded thiolated β-CDs might be a potential drug delivery system for topical scalp diseases.

To face the high tolerance of biofilms to antibiotics, it is urgent to develop new strategies to fight against these bacterial consortia. We describe here an innova-tive antibiofilm nano vector, consisting of a Dispersin B-permethylated-β-cyclodextrin/ciprofloxacin adamantly (DspB-β-CD/CIP-Ad). For this purpose, complexation assays between CIP-Ad and (i) unmodified β-CD and (ii) different derivatives of β-CD, that are 2,3-O-dimethyl-β-CD, 2,6-O-dimethyl-β-CD, and 2,3,6-O-trimethyl-β-CD were tested. A stoichiometry of 1/1 was obtained for the β -CD/CIP-Ad complex by NMR analysis. ITC experiments were carried out to determine Ka, ΔH, ΔS thermodynamic parameters of the complex between β-CD or its different derivatives in the presence of CIP-Ad. A stoichiometry 1/1 of β-CD/CIP-Ad complexes was confirmed with variable affinity according to the type of methylation. A phase solubility study showed increased CIP-Ad solubili-ty with CDs concentration, pointing out complex formation. The evaluation of the antibacterial activity of CIP-Ad and the 2,3-O-dimethyl-β-CD/CIP-Ad or 2,3,6-O-trimethyl-β-CD/CIP-Ad complexes was performed on S.epidermidis strains. MIC studies showed that the complex of CIP-Ad and 2,3-O-dimethyl-β-CD exhibited similar antimicrobial activity to CIP-Ad alone, while the interaction with 2,3,6-O-trimethyl-β-CD increased MIC values. Antimicrobial assays on S. epidermidis biofilms demonstrated that the synergistic effect observed with the DspB/CIP association was partly maintained with the 2,3-O-dimethyl-β-CDs/CIP-Ad complex. To obtain this "all in one" nano vector, able to destroy the biofilm matrix and release the antibiotic simultaneously, we covalently grafted DspB on three carboxylic permethylated CD derivatives with different length spacer arms. The strategy was validated by demonstrating that a DspB-permethylated-β-CD/ciprofloxacin-Ad nanovector exhibited efficient antibiofilm activity.

Twelve overnight fasted, healthy, male volunteers received on separate days a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-cyclodextrin dissolved in the drinking water (250 mL), and (C) 250 mL drinking water containing 25 g alpha-cyclodextrin. Capillary and venous blood samples were collected before breakfast and at regular intervals for a period of 3 hours thereafter. Plasma glucose was determined in capillary blood and plasma insulin in venous blood samples. Breakfast (A) let to the expected rise in blood glucose and insulin concentrations. Breakfast (C) did not produce a significant glycemic and insulinemic response, demonstrating that alpha-cyclodextrin is not hydrolyzed to glucose in the human digestive tract. Mild intestinal symptoms after the ingestion of alpha-cyclodextrin were reported by 4 subjects. The postprandial rises of plasma glucose and insulin were significantly smaller after breakfast (B) than (A). Under the conditions of this study, alpha-cyclodextrin reduced the glycemic and insulinemic index of white bread by 57 and 55 %, respectively. The postprandial time profile of plasma glucose and insulin suggests that, in an initial phase, the digestion of starch is inhibited by alpha-cyclodextrin almost completely. Yet, despite the delayed and reduced digestion of starch, the intake of breakfast (B) was not associated with flatulence or any other gastrointestinal symptoms.

A new polymorph of anhydrous β-cyclodextrin (polymorph III) was obtained and characterized for the first time using powder X-ray diffraction, infrared spectroscopy and thermal analysis. Solution enthalpy and time of dissolution in water were determined by solution calorimetry for this polymorph and compared with those of dried commercial form of β-cyclodextrin (polymorph I), its amorphous form and 2-hydroxypropyl-β-cyclodextrin. Specific heat capacity of polymorphs I and III was determined by differential scanning calorimetry in the wide range of temperatures, which gives enthalpy and Gibbs energy of polymorphic transition at 298 K. Affinity of polymorph III and 2-hydroxypropyl-β-cyclodextrin for water was characterized by determination of their hydration isotherms, which gives the values of hydration Gibbs energy. Being energy-rich, the found new polymorph of β-cyclodextrin has a significantly higher dissolution rate and an in-creased affinity for water compared with the dried commercial form of β-cyclodextrin. Such properties make the new polymorph promising in industrial applications for guest inclusion in aqueous solutions and pastes and may be a desirable alternative for water-soluble β-cyclodextrin derivatives.

Modern medical needs call for the efficient remedies against bacterial diseases including severe pulmonary infections reported as a secondary SARS-Cov-2 infection. Here, we propose imprinted drug ciprofloxacin (CF) into the polymer based on methyl-β-cyclodextrin (MCD) via template synthesis. The obtained polycarbamide nanoparticles possess CF's sustained drug release. The interaction of human serum albumin (HSA) with CF and CF-MCD carriers was conducted by FRET, FTIR, fluorescence, and circular dichroism spectroscopy. These studies uncovered that MCD decreases CF's binding efficiency by 2 times, whereas CF’s encapsulation in polymer matrix doubles the Ka value. The changes in HSA’s secondary structure indicate no alterations in the main mechanism of complex formation between CF and HSA in the presence of MCD-based carries. The drug delivery system demonstrates prolonged CF release at pH 7.4 in presence of HSA (model conditions of blood plasma). CF-MCD carriers inhibit E. coli and B. subtilis growth, but for MAX systems we observed a MIC’s increase (~2 times). We believe that our findings are important for further development of new efficient drug forms.

Drug delivery systems consist of cyclodextrins (CyDs) have kept constant attention for good compatibility, negligible toxicity, and improved pharmacokinetics of drugs. The unique hollow structure has endowed a lot of functions, such as inclusion of guest molecules, functional modification of active hydroxyl groups, and noncovalent interactions. Besides, the polyhydroxy structure has further extended the functions of CyDs by inter/intramolecular interactions and chemical modification. Furthermore, the versatile functions of the complex contribute to physicochemical characteristics alteration of the drugs, therapeutic talent, stimulus-responsive switch, self-assemble capability, and fiber formation. This review attempts to list the recent progress of CyDs and discuss their roles in the drug delivery system. Future perspectives of the construction of CyD-based drug delivery systems are also discussed at the end of this review, which may be the possible directions for the construction of more rational and cost-effective delivery vehicles.

Iloperidone (ILO) is a second-generation antipsychotic drug and a first-line treatment approved by USFDA in May 2009. Iloperidone belongs to Biopharmaceutical Classification Systems (BCS) class II; thus, it is poorly water-soluble, highly permeable, and has pH-dependent solubility. Cyclodextrins and their derivatives have a wide range of applications in different formulations due to their complexation ability, which improves the solubility, stability, safety, and bioavailability of a drug. We have tried the complexation of iloperidone with sulfobutyl ether-β-cyclodextrin (SEβCD) to improve its solubility and dissolution. Complexation was done by the kneading method. The characterization of the SEβCD complexes with Iloperidone was done by FTIR, differential scanning calorimetry (DSC), saturation solubility, etc. A multimedia dissolution of the complex was carried out and compared with the plain drug. A significant improvement in drug release was found from SEβCD complexes in all media when compared with the drug alone.

In this work, we investigated for the first time the complexation of sepiapterin (SP), the natural precursor of the natural essential cofactor tetrahydrobiopterin, that displays mild water-solubility and short biological half-life, with the hydrophobic triacetyl-β-cyclodextrin (TAβCD) to improve its encapsulation within methoxy-poly(ethylene-glycol)-poly(epsilon-caprolactone) (mPEG-PCL) nanoparticles. First, TAβCD-SP complexes were produced by spray-drying of TAβCD/SP binary solutions by utilizing the Nano Spray Dryer B-90 HP. Then, dry powders were characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR) and transmission and scanning electron microscopy (SEM and TEM, respectively) and compared to the complex components and physical mixtures (PMs). Next, SP was encapsulated within methoxy-poly(ethylene-glycol)-poly(epsilon-caprolactone) (mPEG-PCL) nanoparticles by nanoprecipitation of a SP/TAβCD complex/mPEG-PCL solution. In addition to complex nanoencapsulation, we assessed encapsulation of pure SP by nanoprecipitation with an intermediate step, which comprised the co-drying of SP, TAβCD and mPEG-PCL copolymer solution in organic solvent; this step aimed to promote the formation of molecular interactions between SP, TAβCD and the PCL blocks in the copolymer. SP-loaded mPEG-PCL nanoparticles were characterized by dynamic light scattering (DLS) and SEM. Nanoparticles with size of 74-75 nm and small polydispersity index (PDI <0.1) were obtained when SP-TAβCD equimolar spray-dried complex was used for nanoencapsulation, and SEM analysis indicated the absence of free SP crystals. Moreover, the encapsulation efficiency (%EE) and drug loading (DL) were 85% and 2.6%, respectively, as opposed to those achieved with pure SP encapsulation (14% and 0.6%, respectively). Overall, our results confirm that spray-drying of SP/TAβCD solutions at the appropriate molar ratio leads to the hydrophobization of the relatively hydrophilic SP molecule, enabling its encapsulation within mPEG-PCL nanoparticles.

In this study, we aim to evaluate how cyclodextrin molecules affect the hydrophilicity and selec-tivity of PVDF membrane. Herein, we prepared PVDF-PVP(1-x) β-CDx membranes, with x rang-ing from 0 to 1 wt%. The membranes were deeply characterized by means of X-ray diffraction (XRD), attenuated total reflectance infrared (ATR-IR), Raman spectroscopies, Thermal gravimet-ric analysis (TGA), Contact angle measurement (CA), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The study unequivocally demonstrates the effectiveness of the addition of β-CD molecules on membranes' structural, morphological, and dielectric properties. Adding 0.25wt% β-CD enhanced hydrophilicity, with CA decreasing from 72.6° to 56° and roughness decreasing from 81 to 29 nm. The PVDF-PVP(1-x) β-CDx membranes were then fully characterized using electrochemical impedance spectroscopy (EIS) to determine their dielectric properties, which clearly showed that the presence of β-CD induced polarization of the mem-brane. The separation of various dyes with different sizes and charges was utilized. These dyes included methylene blue (MB, positive, 0.504 nm), methyl red (MR, neutral, 0.487 nm), rose Bengal (RB, negative, 0.588 nm), and brilliant blue (BB, negative, 0.798 nm). Based on our re-search, we found that the membrane's selectivity is determined by both exclusion factors (such as size and dielectric properties) and inclusion inside the β-CD cage. We found that using alpha-CD instead of beta-CD led to the disappearance of dye inclusion. These findings strongly sug-gest that β-CD molecules can be a viable solution for dye removal from wastewater.

Ocular pathologies present significant challenges in achieving effective therapeutic re-sults due to various anatomical and physiological barriers. Natural products, such as flavonoids, alone or in association with allopathic drugs, present many therapeutical actions, including anti-cancer, anti-inflammatory, and antibacterial action. However, their clinical employment is chal-lenging for scientists due to their low water solubility. In this study, we designed a liquid formu-lation based on rutin/sulfobutylether-β-cyclodextrin (RTN/SBE-β-CD) inclusion complex for treating ocular infections. The correct stoichiometry and the accurate binding constant were de-termined by employing the SupraFit software on the Uv-vis titration experiment. A deep physical-chemical characterization of the RTN/SBE-β-CD inclusion complex was also performed; it con-firmed the predominant formation of a stable complex (Kc, 9660 M−1) in a 1:1 molar ratio, with high water solubility of 20 times (2.5 mg/mL) higher than the free molecule (0.125 mg/mL), per-mitting the dissolution of the solid complex within 30 min. NMR studies revealed the involve-ment of the bicyclic flavonoid moiety in the complexation, which was also confirmed by molecu-lar modeling studies. In vitro, the antibacterial and antibiofilm activity of the formulation was assayed against Staphylococcus aureus and Pseudomonas aeruginosa strains demonstrating a sig-nificant activity of the formulation to the free components.

The basic hydrolysis of Malachite Green in the presence of β-Cyclodextrin has been studied and a catalytic effect has been found. Indeed, this basic hydrolysis is catalyzed by the interaction of deprotonated cyclodextrin hydroxyl group with the carbocation in the host-guest complex. This behavior is like the hydrolysis of Cristal Violet in the same reaction media.

The aim of this study is to prepare redox-sensitive nanophotosensitizers for targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via disulfide bond creating nanophotosensitizers that were fabricated for redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize suc-cinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss) and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). Chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by dialysis procedure. They formed small particles with an average particle size of 152.0±23.2 nm and they showed improved singlet oxygen (SO) generation in the aqueous solution under light irradiation and was significantly higher than that of Ce6 alone. Ce6 release rate from bCDsu-ss-Ce6 nanophotosensitizers was accelerated by addition of glutathione (GSH), indicating that bCDsu-ss-Ce6 nanophotosensitizers have re-dox-sensitive photosensitizer delivery capacity. bCDsu-ss-Ce6 nanophotosensitizers have low in-trinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, bCDsu-ss-Ce6 nanophotosensitizers showed improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production and phototoxicity compared to those of Ce6 alone. GSH addition resulted in higher Ce6 uptake ratio, ROS generation and phototoxicity than those of Ce6 alone, indicating that bCDsu-ss-Ce6 nanophotosensitizers have redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. At tumor xenograft model using HeLa cells, bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than normal organs, i.e. fluores-cence intensity in tumor tissues was significantly higher than those of other organs while Ce6 alone did not specifically target tumor tissue. These results indicated higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, by efficiently inhibiting growth of tumor in in vivo animal tumor xenograft study.

With the development of health service, animal husbandry, aquaculture and chemical industry, more and more pollutants are discharged into the water environment, including antibiotics and heavy metal ions. These hazard substances pose a great threat to environment safety and human health. As two kinds of new green solvents, ionic liquids (ILs) and deep eutectic solvents (DESs) are widely used in various fields including separation and environmental engineering, which are attracting huge attention from academia and industry. In this study, the optimal ionic liquid and deep eutectic solvent were selected and their complex with β-cyclodextrin (β-CD) were firstly prepared by simple and effective inclusion way. After necessary characterization and analysis, two kinds of complex were applied to prepare a special sorbent disc with two different sides by adding diluent (excipient) and pressing under 5~15 MPa. As the result, the IL and DES could be stably immobilized on the disc and play the key role in selective adsorption for targets. Besides that, the experiments of different hazardous substances achieved the expected results. Based on this study, the complex disc showed a lot of merits in the separation performance, easy preparation and use, simple operation, and good stability. It was believed to be a useful tool for water purification and detection.

β-cyclodextrin-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, we synthesized well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) acted as theranostic nanoparticles for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX) and superparamagnetic iron oxide particles (SPIO) were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to folate receptor-mediated endocytosis process of the nanoparticles and GSH triggered disulfide-bonds cleaving.Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO showed strong MRI contrast enhancement properties. In conclusion, folate-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

Permeability has an important effect on drug absorption. In this study, the effect of different concentrations of sodium sulfobutyl ether-β-cyclodextrin (SBE-β-CD) on the absorption of ranitidine was investigated to examine the mechanism of permeability changes. The results of parallel artificial membrane permeability assay (PAMPA) showed that increasing the concentration of sodium sulfobutyl ether-β-cyclodextrin, 0, 0.12% (w/v), 0.36% (w/v) and 3.6% (w/v), respectively, the apparent permeability coefficient of ranitidine decreased to 4.62×10-5 , 4.5×10-5 , 3.61×10-5 and 1.08×10-5 in Caco-2 cells, respectively. The same results were obtained from oral pharmacokinetic study in rats; Further studies indicated that SBE-β-CD significantly increased the zeta potential of ranitidine. SBE-β-CD interacted with ranitidine charges to form a complex that reduced ranitidine permeability, and SBE-β-CD should be chosen with caution for drugs with poor permeability.

Cyclodextrin (CD) is made up of 7 glucose molecules linked in a ring, creating a cone shape. Its interior can house hydrophobic molecules while the exterior is hydrophilic enough to interact with water molecules. Until now, this feature has been used for the development of active and intelligent packaging applied to food, interacting with the product or its environment to improve one or more aspects of its quality or safety. As well, it is used to provide information on monitoring the time in which food is optimal for consumption, an aspect considered very important for the consumer and for the merchant. A known problem with some of these types of packaging is that the bioactive compounds that are housed in the CD can interact with food and can modify its taste, smell, color and/or texture. Therefore, this review will focus on discerning which packaging is most appropriate for each situation.

Approximately one-third of mankind is chronically exposed to the carcinogenic aflatoxin M1 contained in milk and dairy products and there is no ready to use procedure for decontamination purposes applicable in milk technology. Since β-cyclodextrin is frequently used in food industry, its effect on aflatoxin M1 concentration was investigated during cholesterol removal. So, milk samples were spiked with aflatoxin M1 at the average level 0.89 µg/kg and cholesterol removal was carried out by 2.0% (w/w) β-cyclodextrin addition. As found, average cholesterol concentration decreased by 92.3% while aflatoxin M1 concentration decreased to 0.53 µg/kg, i. e. by 39.1% after the treatment. The procedure itself is easy, inexpensive, and ready to use in milk processing technology on current production lines without any investments, thus fully applicable with a high potential of full aflatoxin M1 milk decontamination efficiency and such way to strengthen considerably the food safety issues associated with milk and dairy products on global level.

Because of lower solubility and considerable metabolism, vardenafil (VRD) bioavailability is 15 %. To get over this obstacle, this study aimed to increase the solubility, hasten the onset of action, and mask the unpleasant taste of VRD utilizing β-cyclodextrin (β-CD) and formulation of the inclusion complex as oral disintegrating tablets (ODTs). The solubility of the obtained complexes in various ratios has been studied. A Box-Behnken design (BBD) was utilized to investigate the influence of excipients on the quality of ODTs. The solubility of VRD was improved at 1:2 drug: β-CD ratio. The formulated VRD-ODTs exhibited satisfying results regarding the hardness and disintegration time. In addition, in vivo taste masking and disintegration time showed improved results, after placing the tablets in the oral cavity of the healthy volunteers. The pharmacokinetic parameters for the optimized VRD–ODTs exhibited a significant improvement with P < 0.05 in the maximum plasma concentration and reduction in the time needed to reach this concentration when compared with the marketed tablets. Finally, the optimized VRD-ODTs exhibited increased oral absorption of VRD and subsequent decreasing the time of onset of clinical effect and masking the unpleasant taste, which is favored for patients with erectile dysfunction.

Human serum albumin (HSA) is multifunctional protein, known to be a natural carrier for a number of endogenous and exogenous compounds, including drugs. Formulating anticancer drugs with HSA is a clinically validated approach to improve the pharmacological properties and provide targeted delivery (passive and active) of cytotoxic payload to the tumor (such as in Abraxane). A number of receptors facilitating HSA uptake from systemic circulation have been characterized. What is interesting, such uptake may differ depending on the nature and quantity of ligands bound to HSA. Based on this, one might like to modify the HSA in a way that its distribution is more favorable for certain therapeutic purposes, thus ensuring more efficient delivery of the therapeutic cargo to disease site. E.g. Levofloxacin (LV), broad spectrum antibiotic drug, could benefit from extended systemic exposure, and stronger interaction with plasma proteins could be useful for this purpose. We have engrafted monomeric or polymeric CDs on the surface of HSA molecules to strengthen the LV adsorption (CD-LV dissociation constant is three orders of magnitude lower than that for HSA-LF). We have found that (HSA-HPolS)conj+LV exhibited the highest activity against E. coli, whereas (HSA-HPCD)conj+LV was the most effective against B. subtilis; and both HSA conjugates were more potent than LV alone or LV with HSA. Further fine-tuning of HSA could yield an improvement in biodistribution, and thus a more favorable risk/benefit ratio.

The functionalization of polymeric substances is of great interest for the development of innovative materials for advanced applications. For many decades, the functionalization of chitosan has been a convenient way to improve its properties with the aim to prepare new materials with specialized characteristics. In the present article, we summarize the latest methods for the modification and derivatization of chitin and chitosan, trying to introduce specific functional groups under experimental conditions, which allow a control over the macromolecular architecture. This is motivated because an understanding of the interdependence between chemical structure and properties is an important condition for proposing innovative materials. New advances in methods and strategies of functionalization such as click chemistry approach, grafting onto copolymerization, coupling with cyclodextrins and reactions in ionic liquids are discussed.

Abstract: Breast cancer is one of the leading causes of death in the female population due to the re-sistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubil-ity and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxy curcumin magnesium complex with cyclodex-trin (DiMeOC-Mg-BCD, 5) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media (PBS) was improved by a factor of 6x over the free metal complex (DiMeOC-Mg). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the MMP-2 and MMP-9, IL-6, and STAT3 expression levels on MDA MB 231 cell lines. Results of an antitumor assay in an in-ovo model showed up to 30% inhi-bition of tumour growth for breast cancer (MDA-MB-231) when using 5 (0.650 mg/Kg dose), and 17.29 % inhibition with the free homoleptic metal complex (1.5 mg/Kg dose, DiMeOC-Mg). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new DiMeOC-Mg-BCD exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

In this paper, corticosteroid–β-cyclodextrin (β-CD) inclusion complexes have been prepared by Supercritical AntiSolvent (SAS) precipitation to enhance the dissolution rate of dexamethasone (DEX) and prednisolone (PRED), which are poorly water-soluble drugs. The processing of the active principles in the absence of a carrier led to the almost complete extraction of the active principle (the small amount of obtained material precipitates in the form of crystals). The coprecipitation of the ingredients in the presence of β-CD was investigated at different concentrations, pressures, and molar ratios. For both the corticosteroids, the optimized operating conditions were 40 °C, 120 bar, an equimolar ratio, and a concentration in DMSO of 20 mg/mL; these conditions led to the attainment of microparticles with a mean diameter equal to 0.197±0.180 μm and 0.131±0.070 μm in the case of DEX and PRED, respectively. The Job’s method confirmed the formation of inclusion complexes in correspondence with the 1/1 mol/mol ratio. Compared to the pure ingredients, the obtained powders have an improved release rate, which is about 3 times faster in both cases.

2-Hydroxypropyl-β-cyclodextrin (HPβCD) has unique properties to enhance the stability and the solubility of low water-soluble compounds by inclusion complexation. Understanding of the structural properties of HPβCD and its derivatives based on the number of 2-hydroxypropyl (HP) substituents at the a-D-glucopyranose subunits is rather important. In this work, replica exchange molecular dynamics simulations were performed to investigate the conformational changes of single- and double-sided HP-substitution called as 6-HPβCDs and 2,6-HPβCDs, respectively. The results show that glucose subunits in both 6-HPβCDs and 2,6-HPβCDs have lower chance to flip than in βCD. Also, HP groups are occasionally blocking the hydrophobic cavity of HPβCDs, thus hindering the drug inclusion. We found that HPβCDs with high number of HP-substitutions are more likely to be blocked, while HPβCDs with double-sided HP-substitution are even more probable to be blocked. Overall, 6-HPβCDs with three and four HP-substitutions are highlighted as the most suitable structures for guest encapsulation based on our conformational analyses such as structural distortion, radius of gyration, circularity and cavity self-closure of the HPβCDs.

Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer’s disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection. This study explores the interplay between cholesterol and HSV-1-induced neurodegeneration. The impact of cholesterol was determined by modulating its levels with methyl-beta-cyclodextrin (MβCD) using the neuroblastoma cell lines SK-N-MC and N2a. We have found that HSV-1 infection triggers the intracellular accumulation of cholesterol in structures resembling endolysosomal/autophagic compartments, a process reversible upon MβCD treatment. Moreover, MβCD exhibits inhibitory effects at various stages of HSV-1 infec-tion, underscoring the importance of cellular cholesterol levels not only in the viral entry pro-cess but also in subsequent post-entry stages. MβCD also alleviated several features of AD-like neurodegeneration induced by viral infection, including lysosomal impairment and intracellu-lar accumulation of amyloid-beta peptide (Aβ) and phosphorylated tau. In conclusion, these findings highlight the connection between cholesterol, neurodegeneration, and HSV-1 infection, providing valuable insights into the underlying mechanisms of AD.