Supramolecular Inclusion Complexes Research Articles

Synthesis of Amylosic Supramolecular Materials by Glucan Phosphorylase-Catalyzed Enzymatic Polymerization According to the Vine-Twining Approach

This article overviews the synthesis of amylosic supramolecular materials through inclusion complexation in glucan phosphorylase (GP)-catalyzed enzymatic polymerization. Amylose is a polysaccharide that is known to form inclusion complexes with a number of hydrophobic small guest molecules. A pure amylose can be synthesized by the enzymatic polymerization of α-d-glucose 1-phosphate monomer with a maltooligosaccharide primer catalyzed by GP. The author has reported that the propagating amylosic chain in the enzymatic polymerization twines around hydrophobic polymers present in aqueous reaction media to form supramolecular inclusion complexes. As it is similar to the way that vines of a plant grow around a rod, this polymerization is termed ‘vine-twining polymerization’. Amylosic supramolecular network materials have been obtained through the vine-twining polymerization by using copolymers, where hydrophobic guest polymers are covalently grafted on hydrophilic main-chain polymers. The enzymatically produced amylosic chains form complexes with the guest polymers among graft copolymers, which act as cross-linking points to form supramolecular networks, resulting in the formation of soft materials, such as gels and films. Vine-twining polymerization using appropriately designed guest polymers has also been performed, which leads to supramolecular products that exhibit new functionality.1 Introduction2 Vine-Twining Polymerization to Form Supramolecular Inclusion Complexes3 Selective Complexation of Amylose toward Guest Polymers in Vine-Twining Polymerization4 Hierarchical Architecture of Amylosic Supramolecular Network Materials by Vine-Twining Polymerization Approach5 Hierarchical Fabrication of Amylosic Supramolecular Materials by Vine-Twining Polymerization Using Designed Guest Polymers6 Conclusions

An investigation into the anti-microbial properties of bacterial cellulose wound dressings loaded with curcumin:hydroxypropyl-β-cyclodextrin supramolecular inclusion complex An investigation into the anti-microbial properties of bacterial cellulose wound dressings loaded with curcumin:hydroxypropyl-β-cyclodextrin supramolecular inclusion complex

Wounds from various sources such as burns and ulcers which have been in a prolonged state of inflammation and rubor, both exudative and non-exudative, are decidedly prone to becoming infected by various opportunistic and commensal microorganisms, both bacterial and fungal due to the warm moist environment at the wound site (Que et al.,2019). The typical approach in treating these wounds is to reduce the level of infection and inflammation, thus encouraging an appropriate environment for successful re-epithelisation resulting in faster healing of the wound. Bacterial cellulose (BC) is an ideal material to produce wound dressings due to the intrinsic properties such as; high chemical stability, high tensile strength and flexibility, large water holding capacity, permeable to gases and liquids, and excellent biocompatibility (Gupta et al., 2016; Gupta et al.,2017, Wahid et al., 2019). In this study, BC produced by Komagataeibacter xylinus was used as a hydrogel matrix and loaded with a well-known antimicrobial agent- curcumin encapsulated in solubility enhancing carriers, hydroxypropyl- β-cyclodextrin (CUR:HPβCD) (Abbas et al., 2019, Gupta et al., 2019). BC was loaded with 2% (w/v) aqueous CUR:HPβCD inclusion complex under constant agitation at 170 rpm at 20°C (room temperature) for 24 hours. Antimicrobial activity was tested against two representative organisms: Candida albicans and Staphylococcus aureus by disc diffusion method. We have previously reported the antibacterial activity of CUR:HPβCD-loaded BC (Gupta et al., 2019). The current study is an extension of our ongoing research where we made an attempt of testing the anti-fungal activity of CUR:HPβCD-loaded BC and compared it with anti-bacterial activity. 8mm discs were aseptically cut and placed on TSA plates seeded with overnight cultures of one of the microorganisms under investigation and incubated at 37°C for 24 hours. The results indicated that C. albicans and S. aureus were both susceptible to CUR:HPβCD inclusion complex with an average zone of inhibition of 12.25±2.2mm and 11±1.2mm respectively (n=4, ±=SD, p <0.05). The results against S. aureus are in accordance with our previously reported findings (Gupta et al., 2019). Current findings support the wound management applications of CUR:HPβCd-loaded BC hydrogels for chronic wounds. References Abbas, M., Hussain, T., Arshad, M., Ansari, A., Irshad, A., Nisar, J., Hussain, F., Masood, N., Nazir, A. and Iqbal, M. (2019). Wound healing potential of curcumin cross-linked chitosan/polyvinyl alcohol. International Journal of Biological Macromolecules, 140, pp.871-876. Gupta, A., Keddie, D., Kannappan, V., Gibson, H., Khalil, I., Kowalczuk, M., Martin, C., Shuai, X. and Radecka, I. (2019). Production and characterisation of bacterial cellulose hydrogels loaded with curcumin encapsulated in cyclodextrins as wound dressings. European Polymer Journal, 118, pp.437-450. Gupta, A., Low, W., Britland, S., Radecka, I. and Martin, C. (2017). Physicochemical characterisation of biosynthetic bacterial cellulose as a potential wound dressing material. British Journal of Pharmacy, 2(2), pp.S37-S38. Gupta, A., Low, W., Radecka, I., Britland, S., Mohd Amin, M. and Martin, C. (2016). Characterisation and in vitro antimicrobial activity of biosynthetic silver-loaded bacterial cellulose hydrogels. Journal of Microencapsulation, 33(8), pp.725-734. Que, A., Nguyen, N., Do, N., Nguyen, N., Tran, N. and Le, T. (2019). Infection of burn wound by Aspergillus fumigatus with gross appearance of fungal colonies. Medical Mycology Case Reports, 24, pp.30-32. Wahid, F., Hu, X., Chu, L., Jia, S., Xie, Y. and Zhong, C. (2019). Development of bacterial cellulose/chitosan based semi-interpenetrating hydrogels with improved mechanical and antibacterial properties. International Journal of Biological Macromolecules, 122, pp.380-387.

Study of supramolecular inclusion complexes of pseudoephedrine, lupinine, anabasine and cytisine with β-cyclodextrin by NMR spectroscopy

Study of supramolecular inclusion complexes of pseudoephedrine, lupinine, anabasine and cytisine with β-cyclodextrin by NMR spectroscopy

Production and characterisation of bacterial cellulose hydrogels loaded with curcumin encapsulated in cyclodextrins as wound dressings

Natural bioactive materials with wound healing properties such as curcumin are attracting interest due to the emergence of resistant bacterial strains. The hydrophobicity of curcumin has been counteracted by using solubility enhancing cyclodextrins. Hydrogels facilitate wound healing due to unique properties and 3D network structures which allows encapsulation of healing agents. In this study, biosynthetic cellulose produced by Gluconacetobacter xylinus (ATCC 23770) was loaded with water soluble curcumin:hydroxypropyl-β-cyclodextrin supramolecular inclusion complex produced by a solvent evaporation method to synthesise hydrogel dressings. The ratios of solvents to solubilise curcumin and hydroxypropyl-β-cyclodextrin were tested for the production of the inclusion complex with optimum encapsulation efficacy. The results confirmed that hydroxypropyl-β-cyclodextrin enhanced the aqueous solubility of curcumin and allowed loading into bacterial cellulose hydrogels. These hydrogels were characterised for wound management applications and exhibited haemocompatability, cytocompatability, anti-staphylococcal and antioxidant abilities and therefore support the potential use of the curcumin:hydroxypropyl-β-cyclodextrin-loaded-bacterial cellulose as hydrogel dressings.

Formation of Supramolecular Soft Materials from Amylosic Inclusion Complexes with Designed Guest Polymers Obtained by Vine-Twining Polymerization.

Amylose forms supramolecular inclusion complexes with polymeric guests in the phosphorylase-catalyzed enzymatic polymerization field, so-called “vine-twining polymerization”. However, such inclusion complexes have not exhibited specific properties and processability as functional supramolecular materials. In this study, we found that amylosic inclusion complexes, which were obtained by vine-twining polymerization using a designed guest polymer, that is, an amphiphilic triblock copolymer poly(2-methyl-2-oxazoline-block-tetrahydrofuran-block-2-methyl-2-oxazoline), exhibited gel and film formation properties. The characterization results of the products suggested that enzymatically elongated amylose chains complexed with the polytetrahydrofuran block in the triblock copolymer. Accordingly, the outer poly(2-methyl-2-oxazoline) blocks constructed hydrophilic spaces among the inclusion complex segments. Furthermore, the presence of such outer blocks affected the lower regularity of crystalline alignment among the inclusion complex segments in the products. Such higher-order structures probably induced the formation of supramolecular soft materials, such as gels and films.

Studying the Dielectric Properties of the Curcubituril Cavity on the Basis of the Solvatochromic Effect of Styryl Dye upon the Formation of an Inclusion Complex

A new approach to the theoretical evaluation of the local dielectric properties of media that contain an organic dye acting as a nanoprobe is proposed. The method is checked so as to evaluate the dielectric properties of the host molecule in a supramolecular inclusion complex from the experimentally measured shift of the optical absorption spectrum of the guest molecules (dye) after the complex formation. Using the Onsager–Liptay model, the dielectric properties of the cucurbit[7]uril cavity was theoretically estimated by analyzing the experimentally measured shift of the absorption spectrum of 1-(3-ammoniopropyl)-4-[(E)-2-(3,4-dimethoxyphenyl)-ethenyl]-pyridinium dication of the dye after it forms a complex with cucurbit[7]uril in an aqueous solution. To parameterize the Onsager–Liptay equation, the positions of the absorption spectral maxima of the dye under study were experimentally measured in the following solvents with known dielectric and optical properties: methanol, ethanol, 1-propanol, 1-butanol, and water. When calculating molecular structures, dipole moments of the ground and excited states, and polarizability, the TD-DFT quantum chemical method with the CAM-B3LYP functional in the 6-311G(d,p) basis set was used within the Gamess (United States) software package. The obtained theoretical value of the effective dielectric permittivity of the cavity (about 13) is in good agreement with the published value.

Improvement of surface hydrophilicity and biological sample-compatibility of molecularly imprinted polymer microspheres by facile surface modification with α-cyclodextrin

Molecularly imprinted polymers (MIPs) compatible with complex biological samples hold much promise in many bioanalytical and biomedical applications and development of new strategies for obtaining such advanced synthetic receptors is thus of high interest. Herein, a facile and efficient new approach is presented for the preparation of MIP microspheres capable of selectively recognizing small organic analyte in the complex biological sample, which involves the simple surface modification of MIP particles bearing polyethylene glycol (PEG) brushes with α-cyclodextrin (α-CD). The proof-of-principle was demonstrated by the first synthesis of propranolol-imprinted polymer microspheres bearing PEG brushes of different molecular weights (Mn = 2000 and 5000) via our previously developed reversible addition-fragmentation chain transfer (RAFT) coupling chemistry, their supramolecular inclusion complexation with α-CD, and subsequent chemical crosslinking. The chain length of the surface-grafted PEG brushes showed much influence on the water-compatibility of MIPs. Whereas the MIP particles bearing PEG brushes of Mn = 2000 hardly showed specific template bindings in both pure water and pure milk, those bearing PEG brushes of Mn = 5000 exhibited moderate specific template bindings in pure water. Nevertheless, the latter MIP particles still failed to show enough specific template bindings in pure milk. The inclusion of α-CD onto PEG brushes proved to largely enhance the surface hydrophilicity of MIPs and lead to their much improved water-compatibility. In particular, the MIP microspheres bearing α-CD-modified PEG brushes of Mn = 5000 showed excellent specific template bindings in both pure water and pure milk. The above strategy not only paves the way for efficiently preparing biological sample-compatible MIPs, but also opens the possibility of generating many other advanced biomaterials with high antifouling properties.

On the encapsulation of Olsalazine by β-cyclodextrin: A DFT-based computational and spectroscopic investigations.

In this work, the supramolecular host-guest interaction of the prodrug Olsalazine (OLZ) and β-Cyclodextrin (β-CD) was examined experimentally and computationally. Experimentally, employing the UV-Vis spectroscopic method in aqueous media at various pH's, results obtained using the Benesi-Hilderbrand approach demonstrated that OLZ can form supramolecular inclusion complex with β-CD with stoichiometric ratio of 1:1. Furthermore, these results revealed that the formation of OLZ: β-CD complexes exhibited insignificant pH dependency in the range 5-8 with an average binding constant (Kb) of approximately 1×103M-1. Computationally, geometry optimization of 1:1 OLZ: β-CD complexes was performed employing the ONIOM (DFT((ωB97XB)/6-31+G(d)),SQM(PM3)) approach. Obtained results demonstrated that OLZ: β-CD complex is stabilized by the formation of intermolecular hydrogen bonds with an average length of approximately 1.8Å. Additionally, the stability of OLZ: β-CD complex was demonstrated employing ADMP molecular dynamic simulations over a timeframe of 500fs. The molecularity of the supramolecular host-guest interaction between OLZ and β-CD is presented and interpreted in the essence of TD-DFT and molecular orbitals analyses.

The preparation and characterization of n-B18H22-beta cyclodextrin inclusion complex

Anti- B18H22 (n-B18H22) is a new class of laser materials. In this paper, n-B18H22-β-cyclodextrin (β-CD) supramolecular inclusion complex was prepared by saturated aqueous solution method for the first time. The characterization of the inclusion complex was studied by FTIR, XRD, and SEM. The results showed that the stability of n-B18H22 in water was greatly enhanced due to the formation of the inclusion complex. This paper has opened a new way to improve the stability and extend the application of n-B18H22 in aqueous solution. The inclusion compound has potential applications in the preparation of borane liquid laser and the synthesis of n-B18H22 derivatives.

Исследование диэлектрических свойств полости кукурбитурила на основе эффекта сольватохромизма стирилового красителя при образовании комплекса включения

AbstractA new approach to the theoretical evaluation of the local dielectric properties of media that contain an organic dye acting as a nanoprobe is proposed. The method is checked so as to evaluate the dielectric properties of the host molecule in a supramolecular inclusion complex from the experimentally measured shift of the optical absorption spectrum of the guest molecules (dye) after the complex formation. Using the Onsager–Liptay model, the dielectric properties of the cucurbit[7]uril cavity was theoretically estimated by analyzing the experimentally measured shift of the absorption spectrum of 1-(3-ammoniopropyl)-4-[(E)-2-(3,4-dimethoxyphenyl)-ethenyl]-pyridinium dication of the dye after it forms a complex with cucurbit[7]uril in an aqueous solution. To parameterize the Onsager–Liptay equation, the positions of the absorption spectral maxima of the dye under study were experimentally measured in the following solvents with known dielectric and optical properties: methanol, ethanol, 1-propanol, 1-butanol, and water. When calculating molecular structures, dipole moments of the ground and excited states, and polarizability, the TD-DFT quantum chemical method with the CAM-B3LYP functional in the 6-311G(d,p) basis set was used within the Gamess (United States) software package. The obtained theoretical value of the effective dielectric permittivity of the cavity (about 13) is in good agreement with the published value.

Supramolecular drug inclusion complex constructed from cucurbit[7]uril and the hepatitis B drug Adefovir

ABSTRACTThe interaction between cucuribit[7]uril (Q[7]) and Adefovir (ADV) has been studied in aqueous solution by 1H NMR spectroscopy, electronic absorption spectroscopy, Isothermal Titration Calorimetry and mass spectrometry. The results revealed that an inclusion complex was formed via encapsulation of the purine rings of the guest ADV, while the phosphonomethoxyethyl group was prevented from entering the cavity. ITC data revealed that the formation of this 1:1 inclusion complex is mainly driven by favourable enthalpy changes. Studies investigating the release of ADV from the inclusion complex revealed enhanced rates under acidic conditions, although the rates were slower than observed for the free guest under the same conditions. Thermal stability studies indicated that the included form of ADV was more stable that the free form.

Supramolecular complexation of polysulfides by β-cyclodextrin polymer functionalized graphene hybrid cathode for high-performance lithium-sulfur batteries

Lithium-sulfur (Li-S) batteries have currently attracted wide attention due to their high energy density of 2600 Wh kg−1 and low costs. However, commercial applications of Li-S batteries still have been hindered by several issues, such as low sulfur utilization, self discharge, low efficiency, and poor cycling stability mainly caused by shuttle effect. β-Cyclodextrins (β-CDs) are well-known supramolecular hosts, capable of including hydrophobic molecules inside their large cavities. Taking advantage of the remarkable molecular recognition properties of β-CDs, they are thus expected to effectively suppress shuttle effect by dynamically forming supramolecular inclusion complexes with the polysulfides. Here, we introduce a new strategy of using β-cyclodextrin polymers (β-CDPs) as supramolecular receptors chemically grafted onto reduced graphene oxide nanosheets (rGO) to construct ternary supramolecular nanostructure of rGO@CDP@S hybrid cathode for Li-S batteries. Interestingly, this proof-of-concept model system has successfully demonstrated reversible capture and release of lithium polysulfides to confine an unfavorable polysulfide shuttle effect via supramolecular host-guest interaction in Li-S batteries. Furthermore, interaction mechanism between β-CD and polysulfide was deeply investigated at the molecular level. More importantly, the {cyclodextrin/polysulfide} supramolecular inclusion complex was first isolated and fully characterized with a wide range of spectroscopic experiments and computational studies. The cyclodextrins-modified graphene-base sulfur cathode rGO@β-CDP@S exhibits remarkably enhanced electrochemical performances in terms of higher specific capacity (1329 mA h g−1 at 0.1 C), rate capability (387 mA h g−1 at 5.0 C), and excellent cycle life (capacity decay rate of 0.040% and 0.053% per cycle after 1000 cycles at 2.0 and 3.0 C), compared to pristine graphene-coated rGO@S composite. Moreover, it enables good cycling performance of high-sulfur-loading cathodes (S mass-loading of 5.3 mg cm−2) achieving discharge capacity of 560 mAh g−1 (Areal capacities: 3.0 mA h cm-2) at 0.2 C after 100 cycles. The results open up a rational approach to shed new lights on designing new functional molecular materials as cathodes for Li–S batteries.

Bioavailability and structural study of 20-hydroxyecdysone complexes with cyclodextrins

20-Hydroxyecdysterone – (2β,3β,5β,22R)-2,3,14,20,22,25-hexahydroxycholest-7-en-6-one was isolated in satisfactory yield using ethanol extraction from the aerial part of Silene wolgensis (Hornem.) Otth; sometimes Silene wolgensis (Willd.) Bess. ex Spreng. The complexation of the phytoecdysteroid with β-cyclodextrin was studied by NMR spectroscopy. By studying the changes in chemical shifts of protons of substrates and receptors it was found that ecdysterone interacts with cyclodextrins to form supramolecular inclusion complexes of stoichiometric composition of 1:1 or 1:2. Ecdysterone-β-cyclodextrin complexes exhibit 100 times higher solubility in water than the parent compound.

Difference in Macroscopic Morphologies of Amylosic Supramolecular Networks Depending on Guest Polymers in Vine-Twining Polymerization.

Amylose, a natural polysaccharide, acts as a host molecule to form supramolecular inclusion complexes in its enzymatically formation process, that is, phosphorylase-catalyzed enzymatic polymerization using the α-d-glucose 1-phosphate monomer and the maltooligosaccharide primer, in the presence of appropriate guest polymers (vine-twining polymerization). Furthermore, in the vine-twining polymerization using maltooligosaccharide primer-grafted polymers, such as maltoheptaose (G7)-grafted poly(γ-glutamic acid) (PGA), in the presence of poly(ε-caprolactone) (PCL), the enzymatically elongated amylose graft chains have formed inclusion complexes with PCL among the PGA main-chains to construct supramolecular networks. Either hydrogelation or aggregation as a macroscopic morphology from the products was observed in accordance with PCL/primer feed ratios. In this study, we evaluated macroscopic morphologies from such amylosic supramolecular networks with different guest polymers in the vine-twining polymerization using G7-grafted PGA in the presence of polytetrahydrofuran (PTHF), PCL, and poly(l-lactide) (PLLA). Consequently, we found that the reaction mixture using PTHF totally turned into a hydrogel form, whereas the products using PCL and PLLA were aggregated in the reaction mixtures. The produced networks were characterized by powder X-ray diffraction and scanning electron microscopic measurements. The difference in the macroscopic morphologies was reasonably explained by stabilities of the complexes depending on the guest polymers.

Elucidation of the mechanism of complexation between oncocalyxone A and cyclodextrins by isothermal titration calorimetry and molecular modeling

The physicochemical stability and bioavailability of oncocalyxone A (onco A), a quinone isolated from Auxemma oncocalyx tree, could be improved by supramolecular inclusion complexes with cyclodextrins (CDs). The aim of this study was thus to elucidate the complexation of onco A with different CDs using isothermal titration calorimetry (ITC) and molecular modeling. Data from the most favorable host:guest interaction made it possible to obtain onco A:HP-γ-CD inclusion complex, which was characterized by FTIR, 1HNMR, DSC and TG. Experimental results showed that onco A tends to interact more favorably with HP-γ-CD (K = 3175 M−1) with the most favorable Gibbs free energy (ΔG = −19.98 kJ.mol−1). Thermodynamic analysis indicates that the formation of the inclusion complex was entropy-driven (-TΔS = −19.54 kJ.mol−1), associated mainly with the hydrophobic interactions and release of water molecules from the cavity of the CD. Taken together, physicochemical analysis showed host:guest intermolecular interactions between onco A and the cavity of the HP-γ-CD, thereby confirming the formation of the inclusion complex. Moreover, molecular docking results showed two main orientations in which the interaction of the hydroxyl group and a hydroxymethyl group at the wider rim of the HP-γ-CD was more stable (average docking energy of −7.3 kcal/mol) than the one involving the methoxy group with two carbonyl groups at the wider rim (−7.1 kcal/mol). In conclusion, onco A:HP-γ-CD inclusion complex based on results of rational approaches was obtained for use in for further pharmaceutical application in drug delivery systems in cancer therapy.

Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine.

Rilpivrine is BCS class II drug used for treatment of HIV infection. The drug has low aqueous solubility (0.0166mg/ml) and dissolution rate leading to low bioavailability (32%). Aim of this work was to enhance solubility and dissolution of rilpivirine using beta-cyclodextrin-based nanosponges. These nanosponges are biocompatible nanoporous particles having high loading capacity to form supramolecular inclusion and non-inclusion complexes with hydrophilic and lipophilic drugs for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonyl diimidazole and pyromellitic dianhydride to prepare nanosponges. The nanosponges were loaded with rilpivirine by solvent evaporation method. Binary and ternary complexes of drug with β-CD, HP-β-CD, nanosponges, and tocopherol polyethylene glycol succinate were prepared and characterized by phase solubility, saturation solubility in different media, in vitro dissolution, and in vivo pharmacokinetics. Spectral analysis by Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry was performed. Results obtained from spectral characterization confirmed inclusion complexation. Phase solubility studies indicated stable complex formation. Saturation solubility was found to be 10-13-folds higher with ternary complexes in distilled water and 12-14-fold higher in 0.1N HCl. Solubility enhancement was evident in biorelevant media. Molecular modeling studies revealed possible mode of entrapment of rilpivirine within β-CD cavities. A 3-fold increase in dissolution with ternary complexes was observed. Animal studies revealed nearly 2-fold increase in oral bioavailability of rilpivirine. It was inferred that electronic interactions, hydrogen bonding, and van der Waals forces are involved in the supramolecular interactions.

Host-guest interaction study of Efavirenz with hydroxypropyl‑β‑cyclodextrin and l‑arginine by computational simulation studies: Preparation and characterization of supramolecular complexes

The present study demonstrates the solubility and dissolution enhancement of Efavirenz (EFV) through preparation of supramolecular inclusion complexes. The supramolecular system comprising of EFV, hydroxypropyl‑β‑cyclodextrin (HP-β-CD) and l‑Arginine was prepared by physical mixing and spray drying methods. The complexes were characterized by powder X-ray diffraction, differential scanning calorimetry, 1H NMR spectroscopy and FT-IR spectroscopy to study alteration in crystallinity of drug. Intrinsic stability constant values (Kc) and complexation efficiency (CE) of HP-β-CD was substantially enhanced due to addition of l‑Arginine. Improved solubility and dissolution was evidenced in the supramolecular system than binary system of EFV and HP-β-CD. Computational modelling and molecular dynamics study revealed that l‑Arginine increased the stability of the complex by bridging between the EFV and the HP-β-CD. It also confirmed that l‑Arginine was positioned on the outer surface of complex and improved polar surface of inclusion complex resulting in increased solubility of the complex. Thus, supramolecular inclusion complexes of EFV with HP-β-CD and l‑Arginine could contribute as an innovative outcome in formulation development of EFV through solubility and dissolution enhancement.

Optical Methods for the Analysis of the Temoprofin Photosensitizer Distribution Between Serum Proteins and Methyl-β-Cyclodextrin Nanocarriers in Blood Serum

Various optical methods for the analysis of the processes leading to temoporfin photosensitizer distribution between supramolecular nanosized inclusion complexes derived from β−cyclodextrins and blood serum proteins were examined. Methods involving induced circular dichroism, fluorescence anisotropy, and the variability of the shape of the photosensitizer fluorescence excitation spectra were compared with traditional methods such as gel chromatography and ultracentrifugation. The feasibility of using the photosensitizer optical characteristics for analyzing both equilibrium and kinetic processes of photosensitizer distribution in blood was demonstrated. The main advantages and limitations of these approaches in in vitro experiments were described.

Supra-molecular inclusion complexation of ionic liquid 1-butyl-3-methylimidazolium octylsulphate with α- and β-cyclodextrins

Host-guest complexation between ionic liquid (IL) 1-butyl-3-methylimidazolium octylsulphate [Bmim][OS] and cyclodextrins (α- and β- CDs) have been studied. Surface tension, conductivity measurements revealed the formation of 1:1(M) stoichiometry for inclusion complexes (ICs) and further confirmed by UV–Visible and FT-IR results. The nature of the complexes has been established using interfacial and thermodynamic parameters. The aggregation number, Stern-Volmer constants, association constants were obtained from fluorescence quenching and Benesi-Hildebrand methods. The critical micelle concentration (cmc) and association constants of [Bmim][OS] are higher for β-CD as compared to α-CD. FT-IR spectra indicated that CDs and [Bmim][OS] could from ICs with stoichiometry 1:1(M).

Folate receptor targeted bufalin/β-cyclodextrin supramolecular inclusion complex for enhanced solubility and anti-tumor efficiency of bufalin

Bufalin (BF), a traditional Chinese medicine, exhibited inhibitory activities against a broad spectrum of tumor cells. The present study elaborates that bufalin was successfully encapsulated into the cavity of β-cyclodextrin (β-CD), which was determined by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1H NMR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The best reaction mole ratio of BF/β-CD was 1:5. The solubilities of bufalin in water and phosphate buffer solution (pH=7.4) were increased up to 24 and 34 times after encapsulated into the cavity of β-CD respectively. The inclusion efficiency (IE) and drug loading (DL) of bufalin in the inclusion complex were (94.22±0.85)% and (14.11±0.20)%, respectively. Then β-CD conjugated with folic acid (FA) were further prepared and employed to improve the anti-tumor efficacy of inclusion complex. The in vitro dissolution and solubility study showed better values of inclusion complex and FA targeted inclusion complex than that of pure BF. Cytotoxicity experiments by using HCT116 cell line revealed that the antitumor efficiency of bufalin were enhanced more than two folds in the presence of β-CD and folate conjugated β-CD (FA-PEI-β-CD), which demonstrated the potential application of β-CD (FA-PEI-β-CD) as delivery vehicles of bufalin for antitumor therapy.