Polyrotaxane (PR) has garnered increasing attention due to its unique structure and exceptional performance. In this study, a polypseudorotaxane (PPR) initiator was prepared through the self-assembly of bromine-capped Pluronic F68 and β-cyclodextrins (β-CD) in water. Polyrotaxane-containing triblock copolymers (PR copolymers) were successfully synthesized by atom transfer radical polymerization (ATRP) of butyl methacrylate (BMA) using the PPR initiator in the presence of Cu(I)Br/PMDETA. The structure of the PR copolymers was thoroughly characterized using infrared spectroscopy (IR), proton nuclear magnetic resonance (1H NMR), and gel permeation chromatography (GPC). The mobility of β-CD in the PR copolymers was demonstrated through dielectric measurements. Mechanical tests, including tensile strength assessments, thermal mechanical analysis, and dynamic mechanical analysis, confirmed the excellent mechanical properties and good processability of the PR copolymer, attributed to the PBMA blocks. Furthermore, the mechanical properties were found to be modulated by the motility of the threaded β-CDs. Consequently, the superior mechanical properties and the high mobility of the threaded β-CDs suggest promising potential for the as-prepared PR polymer in various advanced applications.

OBJECTIVE: Raloxifene hydrochloride (RLX) is used extensively in the treatment of osteoporosis, only 2% of RLX\'s bioavailability remains after a significant first pass metabolism. Besides coming from BCS class II, RLX is not very soluble in water. Thus, the goal of the current study was to improve RLX solubility by creating an inclusion complex using β cyclodextrin (β-CD) as a carrier and solid dispersion with Poloxamer 407.
METHODS: Inclusion complex and solid dispersion were made using a variety of techniques, including kneading, co-precipitation, and physical mixing and solid dispersion using different drug to carrier ratios (1:1, 1:2 and 1:3).
RESULTS: Inclusion complex made using the co-precipitation method had shown 9-fold improvements in water solubility when compared with plain RLX. In order to assess the optimized complex\'s compatibility, thermal analysis, and crystallinity, X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy were used. The XRD and DSC study\'s results indicated that RLX changed from a crystalline to an amorphous state. IC-6 exhibits effective water solubility based on the outcome. However, upon comparison of the two techniques, the β-CD complexation method shown an impressive rise in drug solubility when compared to solid dispersion.

In this comprehensive investigation, a novel pH-responsive hydrogel system comprising mimosa seed mucilage (MSM), β-cyclodextrin (β-CD), and methacrylic acid (MAA) was developed via free radical polymerization technique to promote controlled drug delivery. The hydrogel synthesis involved strategic variations in polymer, monomer, and crosslinker content in fine-tuning its drug-release properties. The resultant hydrogel exhibited remarkable pH sensitivity, selectively liberating the model drug (Capecitabine = CAP) under basic conditions while significantly reducing release in an acidic environment. Morphological, thermal, and structural analyses proved that CAP has a porous texture, high stability, and an amorphous nature. In vitro drug release experiments showcased a sustained and controlled release profile. Optimum release (85.33 %) results were recorded over 24 h at pH 7.4 in the case of MMB9. Pharmacokinetic evaluation in healthy male rabbits confirmed bioavailability enhancement and sustained release capabilities. Furthermore, rigorous toxicity evaluations and histopathological analyses ensured the safety and biocompatibility of the hydrogel. This pH-triggered drug delivery system can be a promising carrier system for drugs involving frequent administrations.

OBJECTIVE: The primary limitations of tadalafil in treating erectile dysfunction are its low solubility and unpleasant bitter taste, which ultimately result in inadequate patient adherence. The present study aimed to develop and characterize a medicated chocolate formulation containing Tadalafil and ß-CD (solubility enhancer) employing the concept of Design of Experiment (DoE) using chocolate as a user-friendly excipient.
METHODS: An inclusion complex was formulated by incorporating the drug into ß-CD using the kneading method for solubility improvement and also as a taste masker for Tadalafil. The ratio of drug: ß-CD inclusion complex was selected based on a phase solubility study. The inclusion complex was molded into a chocolate base and optimized using the DoE approach. Further, drug excipient interaction was evaluated by DSC and FTIR study.
RESULTS: Phase solubility study suggested a 1:1 ratio of Tadalafil: β-CD for better solubility. DSC spectra suggested the conversion of crystalline structure into an amorphous state which indicates improvement of the drug solubility. DSC and FTIR studies revealed that there was no significant interaction between drug and excipients. Next, %CDR (cumulative drug release) at 30 min revealed the immediate effect of Tadalafil from chocolate formulation and free drug analysis (an unbound drug with ß-CD) proved reduced bitterness of the drug in the complex. Additionally, the medicated chocolate was found to be stable at room temperature as per stability study.
CONCLUSIONS: β-CD was found to be a promising multifunctional excipient as a solubility enhancement carrier and taste masker for bitter-tasting drugs.

This paper presents the theoretical calculations of the inclusion complex formation between native ceftobiprole, a promising antibiotic from the cephalosporin group, and selected cyclodextrins (CDs) approved by the European Medicines Agency. Ceftobiprole was studied in three protonation states predicted from pKa calculations, along with three selected CDs in a stoichiometric ratio of 1:1. It was introduced into the CD cavity in two opposite directions, resulting in 18 possible combinations. Docking studies determined the initial structures of the complexes, which then served as starting structures for molecular dynamics simulations. The analysis of the obtained trajectories included the spatial arrangement of ceftobiprole and CD, the hydrogen bonds forming between them, and the Gibbs free energy (ΔG) of the complex formation, which was calculated using the Generalised Born Surface Area (GBSA) equation. Among them, a complex of sulfobutyl ether- (SBE-) β-CD with protonated ceftobiprole turned out to be the most stable (ΔG = -12.62 kcal/mol = -52.80 kJ/mol). Then, experimental studies showed changes in the physiochemical properties of the ceftobiprole in the presence of the CDs, thus confirming the validity of the theoretical results. High-performance liquid chromatography analysis showed that the addition of 10 mM SBE-β-CD to a 1 mg/mL solution of ceftobiprole in 0.1 M of HCl increased the solubility 1.5-fold and decreased the degradation rate constant 2.5-fold.

In current work, quince seed mucilage and β-Cyclodextrin based pH regulated hydrogels were developed using aqueous free radical polymerization to sustain Capecitabine release patterns and to overcome its drawbacks, such as high dose frequency, short half-life, and low bioavailability. Developed networks were subjected to thermal analysis, Fourier transforms infrared spectroscopy, powder x-ray diffraction, elemental analysis, scanning electron microscopy, equilibrium swelling, and in-vitro release investigations to assess the network system\'s stability, complexation, morphology, and pH responsiveness. Thermally stable pH-responsive cross-linked networks were formed. Nanocomposite hydrogels were prepared by incorporating Capecitabine-containing clay into the swollen hydrogels. All the formulations exhibited equilibrium swelling ranging from 67.98 % to 92.98 % at pH 7.4. Optimum Capecitabine loading (88.17 %) was noted in the case of hydrogels, while it was 74.27 % in nanocomposite hydrogels. Excellent gel content (65.88 %-93.56 %) was noticed among developed formulations. Elemental analysis ensured the successful incorporation of Capecitabine. Nanocomposite hydrogels released 80.02 % longer than hydrogels after 30 h. NC hydrogels had higher t1/2 (10.57 h), AUC (121.52 μg.h/ml), and MRT (18.95 h) than hydrogels in oral pharmacokinetics. These findings imply that the pH-responsive carrier system may improve Capecitabine efficacy and reduce dosing frequency in cancer therapy. Toxicity profiling proved the system\'s safety, non-toxicity, and biocompatibility.

Using sliver nanoparticles modified with β-cyclodextrin and α-iron oxide (β-CD/α-Fe2O3@AgNPs) as surface-enhanced Raman spectroscopy (SERS) substrate, two sensitive methods for detecting apramycin and kanamycin were established. The synthesized β-CD/α-Fe2O3@AgNPs were characterized through ultraviolet visible (UV-vis) spectroscopy, transmission electron microscope (TEM), X-ray diffraction (XRD) and thermogravimetric analyses (TGA). The interactions of the two drugs and substrate were researched by UV-vis absorption and fourier transform infrared (FT-IR). The linear relationship between apramycin/kanamycin and SERS intensity was observed. The limits of detection (LODs) (S/N = 3) were 3.42 and 0.31 nmol/L. The two SERS methods were effectively applied to detect apramycin and kanamycin in beef samples and commercial injection. The recoveries were 96.84 - 102.20% with relative standard deviations (RSD) of 0.6---4.0% for apramycin and 95.67 - 103.18% with RSD of 1.4 - 2.5% for kanamycin, respectively.

There is huge demand for developing guests that bind β-CD and can conjugate multiple cargos for cellular delivery. We synthesized trioxaadamantane derivatives, which can conjugate up to three cargos per guest. 1 H NMR titration and isothermal titration calorimetry revealed these guests form 1 : 1 inclusion complexes with β-CD with association constants in the order of 103  M-1 . Co-crystallization of β-CD with guests yielded crystals of their 1 : 1 inclusion complexes as determined by single-crystal X-ray diffraction. In all cases, trioxaadamantane core is buried within the hydrophobic cavity of β-CD and three hydroxyl groups are exposed outside. We established biocompatibility using representative candidate G4 and its inclusion complex with β-CD (β-CD⊂G4), by MTT assay using HeLa cells. We incubated HeLa cells with rhodamine-conjugated G4 and established cellular cargo delivery using confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS) analysis. For functional assay, we incubated HeLa cells with β-CD-inclusion complexes of G4-derived prodrugs G6 and G7, containing one and three units of the antitumor drug (S)-(+)-camptothecin, respectively. Cells incubated with β-CD⊂G7 displayed the highest internalization and uniform distribution of camptothecin. β-CD⊂G7 showed higher cytotoxicity than G7, camptothecin, G6 and β-CD⊂G6, affirming the efficiency of adamantoid derivatives in high-density loading and cargo delivery.

BACKGROUND: Ginsenoside Rg5 has been proven to possess numerous health benefits. However, Rg5 is difficult to prepare using the current methods, and the poor stability and solubility of Rg5 are intractable properties that limit its application. We try to establish and optimize a new method for preparing Rg5.
METHODS: Different amino acids acted as catalysts, and reaction conditions were investigated to transform Rg5 in GSLS. Different CDs and reaction conditions were investigated for the preparation of CD-Rg5 based on yield and purity; ESI-MS, FT-IR, XRD and SEM analyses were used to prove the formation of the CD-Rg5 inclusion complex. Both the stability and bioactivity of β-CD-Rg5 were investigated.
RESULTS: The content of Rg5 reached 140.8 mg/g after transformation of GSLS using Asp as a catalyst. The yield of β-CD-Rg5 reached a maximum of 12% and a purity of 92.5%. The results showed that the β-CD-Rg5 inclusion complex can improve its stability of Rg5 against light and temperature. Antioxidant activity analyses against DPPH, ABTS+, and Fe2+ chelation showed enhanced antioxidant activity of the β-CD-Rg5 inclusion complex.
CONCLUSIONS: A novel and effective strategy for the separation of Rg5 from ginseng stem-leaf saponins (GSLS) was developed to improve the stability, solubility, and bioactivity of Rg5.

The effective detoxification of organophosphate (OP) nerve agents (OPNAs) is a challenging issue for scientists. The host-guest inclusion complexes of five V-type nerve agents (VE, VG, VM, VR and VX) with β-cyclodextrin (β-CD) have been studied by combining quantum mechanical (QM) calculations and molecular dynamics (MD) simulations. The frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) have been analyzed to describe the reactivity parameters and electronic properties. The obtained results clearly reveal that stable complexes were formed in both vacuum and water media, and the complexation process occurred spontaneously. To understand non-covalent interactions, natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) have been used. IR and Raman spectra have been calculated to confirm the formation of complexes and also thermodynamic parameters have been investigated. It was demonstrated that in addition to van der Waals interactions, the presence of intermolecular hydrogen bonds enhances the stability of these complexes. Furthermore, MD simulations were carried out to get a better insight into the inclusion process of the above complexes. From MD simulations, all simulated systems reached full equilibration at 1000 ps and the V-agent molecules consistently remained in the β-CD cavity and only had vibrational motion inside the cavity. More importantly, MD simulations support the findings of QM calculations and indicate that hydrogen bonding can help the leaving groups of V-agents to be released and them to be hydrolyzed. All results have shown that the VR agent formed the most stable complex with β-CD molecule than that of other agents.Communicated by Ramaswamy H. Sarma.