Inclusion Complexes Research Articles

Development of a Novel Cyclodextrin-Chitosan Polymer for an Efficient Removal of Pharmaceutical Contaminants in Aqueous Solution.

A novel polymer synthesized by grafting three cyclodextrins onto chitosan was characterized and evaluated for its potential to adsorb two pharmaceutical residues: ibuprofen and progesterone. The influence of various operational parameters, including contact time, initial molecule concentration, pH, ionic strength, and temperature, was investigated. The synthesized polymer exhibits an amorphous and porous structure with a remarkable swelling capacity of 9.5 mmol/g. It demonstrates remarkable adsorption capacities for progesterone and ibuprofen, reaching 90% and 75%, respectively. Kinetic studies reveal that the adsorption of both molecules follows a pseudo-second-order model. A DSC analysis elucidated the adsorption mechanism, which is governed by the formation of inclusion complexes and electrostatic interactions within the polymer network. The polymer's regeneration after 23 cycles demonstrates its sustainable adsorption efficiency. The combination of chitosan with three cyclodextrins opens up promising new avenues for water treatment and the removal of specific pollutants. This approach significantly improves the material's selectivity towards target pollutants, offering a significant advantage in pollution remediation applications.

Prediction of the free energy of binding for cyclodextrin-steroid complexes: phase solubility and molecular dynamics studies

Steroid hormones play a crucial role in the body by acting as chemical messengers. They are, however, poorly soluble in water, and cyclodextrins can increase their solubility thus leading to increased bioavailability when used in drug formulations. Accuracy in the prediction of the free energy of binding of cyclodextrin/steroid inclusion complexes with simulation is important because of the potential value it brings by providing low-cost predictions of the real-life behavior of the cyclodextrin/steroid inclusion complex and the potential for high-through-put screening. Many computational methods exist, and it is therefore important to understand the ability of current theoretical models to accurately predict the free energy of binding for these inclusion complexes. We focused specifically on the estimation of the free energy of binding of inclusion complexes of four steroids: Hydrocortisone, dexamethasone, prednisolone, and 6α-methylprednisolone with native α-CD, β-CD, γ-CD, (2-hydroxy)propyl-β-CD, and sulfobutylether-β-CD by phase solubility as well as with α, β, and γ-CD by simulations. The simulations were assessed with both docking and the molecular mechanics combined with the generalized Born and surface area (MM/GBSA) continuum solvation approach. Considering the phase solubility diagram, (2-hydroxy)propyl-β-CD and sulfobutylether-β-CD dissolved more steroids in the higher concentration range as expected. The assessment of the free energy of binding obtained from the phase solubility and theory showed that the MM/GBSA method has shown promise in reliably generating accurate predictions in the field of calculating the free energy of binding of steroids/cyclodextrins with a correlation coefficient (R2) = 0.94.

Assessment of the usefulness of β-cyclodextrin in the removal of progesterone from the environment

The paper presents the results and interpretation of theoretical calculations for the progesterone–β-cyclodextrin (P@β-CD; G4MP2) and progesterone–β-cyclodextrin–β-cyclodextrin (P@β-CD–β-CD; G2) systems. The geometry of the progesterone molecule was optimized on basis of the DFT theory using the B3LYP, PBE1PBE and M06-2X functionals, for selected Pople basis sets [6-31G, 6‐31++G, 6‐31++G(d,p), 6-311G, 6‐311++G, 6‐311++G(d,p)] and the Dunning basis set (aug-cc-pVDZ). Presented results of theoretical calculations provide insight into the mechanism of formation of supramolecular systems of progesterone and β-cyclodextrin, allowing us to understand the impact of differences in the polarizability of specific fragments of the “guest” molecule, through the analysis of the Mulliken population distribution, on the tendency for equilibrium inclusion by “host” molecules characterized by selective affinity towards hydrophilic and hydrophobic molecular systems. The comparison of model structures of “guest–host” systems with 1:1 and 1:2 stoichiometry allows us to assess the contribution of a given type of non-covalent interactions (hydrogen bonds, van der Waals interactions, London dispersion forces) in the formation of supramolecular complexes. Due to the complexity of the real research object, including interactions between large molecules in solution, in this work it was decided to choose an approximation that reflects only the key effects. The results presented in this paper constitute a starting point for both theoretical research on analogous supramolecular systems based on β-cyclodextrin derivatives, as well as instrumental studies (NMR, FT–IR, HPLC) of preparations of real inclusion complexes. The approach adopted now can contribute to a better understanding of the phenomenon used in the development of water purification technologies.

Supramolecular chemistry in cyclodextrin inclusion complexes: The formation rules of terpenes/β-cyclodextrin inclusion complexes

Supramolecular chemistry of cyclodextrins (CDs) inclusion complexes is a hot research topic at present, but current studies often focus on the host-guest interaction between CDs and hydrophobic substances, while ignoring the self-assembly behavior of the host and guest during the inclusion process. Based on the spatial structures, six representative terpenes were selected in this study, and the stoichiometric ratio between terpenes and β-cyclodextrin (β-CD) was investigated by isothermal titration calorimetry (ITC) method. Meanwhile, the constructed inclusion complexes (ICs) were characterized by nuclear magnetic resonance, X-ray diffraction, scanning electron microscope, etc. On this basis, the assembly process of β-CD and terpenes was investigated firstly by molecular simulation method, and the inclusion process between β-CD and terpenes was further studied in terms of the formation of individual ICs and ICs aggregates. Results showed that hydrophobic interaction and van der Waals force were the main driving forces of the reaction between terpenes and β-CD, and the formation of ICs, β-CD molecule aggregation, terpene aggregation, and ICs aggregation occurred simultaneously during the inclusion process of terpenes and β-CD. To sum up, this study may provide certain thinking and reference for the subsequent supramolecular chemical research on CDs.

A Sodium Germanosilicide with Unusual Network Topology.

The germanosilicide Na4-xGeySi16-y (0.4 ≤ x ≤ 1.1, 4.7 ≤ y ≤ 9.3) was synthesized under high-pressure, high-temperature conditions. The novel guest-host compound comprises a unique tetrel framework with dual channels housing sodium and smaller, empty (Si,Ge)9 units. The arrangement represents a new structure type with an overall structural topology that is closely related to a hypothetical carbon allotrope. Topological analysis of the structure revealed that the guest environment space cannot be tiled with singular polyhedra as in cage compounds (e.g., clathrates). The analysis of natural tilings provides a convenient method to unambiguously compare related tetrel-rich structures and can help elucidate new possible structural arrangements of intermetallic compounds.

Ion Mobility-Mass Spectrometry Strategies to Elucidate the Anhydrous Structure of Noncovalent Guest/Host Complexes.

Structural mass spectrometry (MS) techniques are fast and sensitive analytical methods to identify noncovalent guest/host complexation phenomena for desirable solution-phase properties. Current MS-based studies on guest/host complexes of drug and drug-like molecules are sparse, and there is limited guidance on how to interpret MS information in the context of host nanoencapsulation and inclusion. Here, we use structural MS strategies, combining energy-resolved MS (ERMS), ion mobility-MS (IM-MS), and computational modeling, to characterize 14 chemically distinct drug and drug-like compounds for their propensity to form guest/host complexes with the widely used excipient, beta-cyclodextrin (βCD). The majority (11/14) yielded a 1:1 guest/host complex, and ion mobility collision cross section (CCS) analysis provided subtle evidence of gas-phase compaction of complexes in both polarities. The three distinct dissociation channels observed in ERMS (i.e., charged βCD, charged guest, and partial guest loss) were used to direct charge-site assignments for computational modeling, and structural candidates were prioritized using helium-derived CCS measurements combined with root-mean-square distance analysis. The combined analytical information from ERMS, IM-MS, and computational modeling suggested that the majority of anhydrous complexes are inclusion complexes with βCD. Taken together, this work demonstrates a roadmap for how multiple MS-based analytical measurements can be combined to interpret the structures that guest/host complexes adopt in the absence of water.

Effect of Encapsulated Phenolic Compounds of Cocoa on Growth of Lactic Acid Bacteria and Antioxidant Activity of Fortified Drinking Yogurt.

The aim of this study was to obtain drinking yogurts enriched with ACTICOA cocoa powder (ACTICOA), its extract (EACTICOA) and pure phenolics, as well as their inclusion complexes with cyclodextrins and alginate-chitosan (A-Ch) capsules, and to evaluate the effects of these additives on the viability of lactic acid bacteria (LAB) and antioxidant properties of fresh yogurts and yogurts stored for 14 days at 4 °C. The application of cocoa phenolic compounds in free form and in the form of EACTICOA to yogurts resulted in the greatest increase in the concentration of phenolic compounds and a significant improvement in the antioxidant properties of the fortified products. The highest TPC was found in yogurts enriched with free quercetin (107.98 mg CE/g). Yogurt fortified with free gallic acid showed the highest ability to neutralize free radicals (EC50 = 2.74 mg/mg DPPH, EC50 = 5.40 mg/mg ABTS) and reduce ferric ions (183.48 µM Trolox/g). The enrichment of yogurts with the tested phenolic compounds preparations, especially in the form of encapsulates, did not affect the viability of LAB during storage.

Interstitials in Thermoelectrics.

Defect structure is pivotal in advancing thermoelectric performance with interstitials being widely recognized for their remarkable roles in optimizing both phonon and electron transport properties. Diverse interstitial atoms are identified in previous works according to their distinct roles and can be classified into rattling interstitial, decoupling interstitial, interlayer interstitial, dynamic interstitial, and liquid interstitial. Specifically, rattling interstitial can cause phonon resonance in cage compound to scatter phonon transport; decoupling interstitial can contribute to phonon blocking and electron transport due to their significantly different mean free paths; interlayer interstitial can facilitate out-of-layer electron transport in layered compounds; dynamic interstitial can tune temperature-dependent carrier density and optimize electrical transport properties at wide temperatures; liquid interstitial could improve the carrier mobility at homogeneous dispersion state. All of these interstitials have positive impact on thermoelectric performance by adjusting transport parameters. This perspective therefore intends to provide a thorough overview of advances in interstitial strategy and highlight their significance for optimizing thermoelectric parameters. Finally, the profound potential for extending interstitial strategy to various other thermoelectric systems is discussed and some future directions in thermoelectric material are also outlined.

Investigation of the structural and thermodynamic properties of the inclusion complex of apixaban with natural cyclodextrins

Apixaban (APX) is an anticoagulant drug with poor aqueous solubility, limiting its bioavailability. This study investigates whether solubility can be enhanced by inclusion of APX within the native (α-, β-, and γ-) cyclodextrins (CDs). Phase solubility studies revealed an enhancement in solubility in the presence of β-CD. The complex formation constant for β-CD was found to be one order of magnitude higher than that of α-CD and γ-CD (K11 = 35, 268 and 41 M−1 for α-, β- and γ-CDs, respectively). 1H NMR spectra in DMSO confirmed the formation of the APX/β-CD complex in solution. Infrared (IR) spectroscopy and differential scanning calorimetry (DSC) confirmed the formation of an APX/β-CD inclusion complex in the solid state. Molecular dynamics (MD) simulations were employed to study the dynamics and host-guest interactions of APX with the CDs. MM-PBSA estimates of the binding free energies revealed a higher stability of the complex with β-CD compared to the other two, in agreement with the experimental results, with favorable van der Waals and electrostatic interactions, and with the former contributing much more significantly.

Development of itraconazole ocular delivery system using β-cyclodextrin complexation incorporated into dissolving microneedles for potential improvement treatment of fungal keratitis

Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using β-cyclodextrin (β-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the β-CD was −5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using β-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration.

7-Phenylheptanoic Acid-Hydroxypropyl β-Cyclodextrin Complex Slows the Progression of Renal Failure in Adenine-Induced Chronic Kidney Disease Mice.

The characteristic accumulation of circulating uremic toxins, such as indoxyl sulfate (IS), in chronic kidney disease (CKD) further exacerbates the disease progression. The gut microbiota, particularly gut bacterial-specific enzymes, represents a selective and attractive target for suppressing uremic toxin production and slowing the progression of renal failure. This study investigates the role of 4-phenylbutyrate (PB) and structurally related compounds, which are speculated to possess renoprotective properties in suppressing IS production and slowing or reversing renal failure in CKD. In vitro enzyme kinetic studies showed that 7-phenylheptanoic acid (PH), a PB homologue, suppresses the tryptophan indole lyase (TIL)-catalyzed decomposition of tryptophan to indole, the precursor of IS. A hydroxypropyl β-cyclodextrin (HPβCD) inclusion complex formulation of PH was prepared to enhance its biopharmaceutical properties and to facilitate in vivo evaluation. Prophylactic oral administration of the PH-HPβCD complex formulation reduced circulating IS and attenuated the deterioration of renal function and tubulointerstitial fibrosis in adenine-induced CKD mice. Additionally, treatment of moderately advanced adenine-induced CKD mice with the formulation ameliorated renal failure, although tissue fibrosis was not improved. These findings suggest that PH-HPβCD can slow the progression of renal failure and may have implications for preventing or managing CKD, particularly in early-stage disease.

Structure, stability, and dynamics of inclusion complexes formed from auranofin derivatives and hydroxypropyl-β-cyclodextrin

Structure, stability, and dynamics of inclusion complexes formed from auranofin derivatives and hydroxypropyl-β-cyclodextrin

Crystal structure and cryomagnetic study of a mononuclear erbium(III) oxamate inclusion complex.

The synthesis, crystal structure and magnetic properties of an oxamate-containing erbium(III) complex, namely, tetrabutylammonium aqua[N-(2,4,6-trimethylphenyl)oxamato]erbium(III)-dimethyl sulfoxide-water (1/3/1.5), (C16H36N)[Er(C11H12NO3)4(H2O)]·3C2H6OS·1.5H2O or n-Bu4N[Er(Htmpa)4(H2O)]·3DMSO·1.5H2O (1), are reported. The crystal structure of 1 reveals the occurrence of an erbium(III) ion, which is surrounded by four N-phenyl-substituted oxamate ligands and one water molecule in a nine-coordinated environment, together with one tetrabutylammonium cation acting as a counter-ion, and one water and three dimethyl sulfoxide (DMSO) molecules of crystallization. Variable-temperature static (dc) and dynamic (ac) magnetic measurements were carried out for this mononuclear complex, revealing that it behaves as a field-induced single-ion magnet (SIM) below 5.0 K.

Modulation of the intermolecular interactions of cucurbit[7]uril with phenylalanine derivatives by the functional groups

Abstract Intermolecular interactions in 1:1 inclusion complexes of cucurbit[7]uril (CB[7]) with phenylalanine derivatives were investigated by density functional theory (B97-D) calculations. For each complex, 2 optimized geometries were found: conformer C in which a guest molecule resided in the center of CB[7], and conformer E where a guest molecule was present at the edge of CB[7]. The order of energy differences between these conformers agreed well with previously reported differences in the affinity of guest molecules for CB[7]. Molecular dynamics simulations of the complexes showed that the guest molecules in CB[7] had different stabilities, and the calculated binding free energies between them also qualitatively agreed with the experimental results. Pair-interaction energy decomposition analyses of the complexes at FMO-MP2/6-31G(d) and aug-cc-pVDZ level of theory were performed using snapshot structures at 500 ns of simulations. The dispersion interaction characterized the interaction, and the order of total interaction energies between the guest molecules and CB[7] was also associated with the experimental results. A significant difference in electrostatic interaction energies was observed in conformer E, which was correlated with the stability of the guest molecules at the edge of CB[7]. The balance between the stabilities of these conformers was correlated with the affinity of guest molecules for CB[7].

Cyclodextrin inclusion complex and amorphous solid dispersions as formulation approaches for enhancement of curcumin’s solubility and nasal epithelial membrane permeation

BackgroundCurcumin is a compound that occurs in the rhizomes of the turmeric plant (Curcuma longa) and has shown potential for the treatment of illnesses including certain neurodegenerative diseases. The bioavailability of curcumin is hindered by its extremely poor aqueous solubility.ResultsThis study aimed to apply formulation strategies such as inclusion complex formation with hydroxypropyl-β-cyclodextrin (HPβCD), as well as amorphous solid dispersion (ASD) formation with poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) and hydroxypropyl methylcellulose (HPMC) to increase curcumin’s solubility and thereby its nasal epithelial membrane permeation. The curcumin formulations were evaluated by means of DSC, TGA, FT-IR, XRPD, microscopic imaging, aqueous solubility and membrane permeation across nasal respiratory and olfactory epithelial membranes. The solubility of curcumin was substantially increased by the formulations from 8.4 µg/ml for the curcumin raw material to 79.0 µg/ml for the HPβCD inclusion complex, 256.4 µg/ml for the HPMC ASD and 314.9 µg/ml for the PVP VA64 ASD. The HPMC ASD only slightly changed the membrane permeation of curcumin, while the PVP VA64 ASD decreased the membrane permeation of curcumin. The HPβCD inclusion complex enhanced the nasal epithelial membrane permeation of curcumin statistically significantly across the olfactory epithelial tissue and extensively across the respiratory epithelial tissue.ConclusionComplexation of curcumin with HPβCD enhanced the solubility of curcumin and thereby also increased its permeation across excised nasal respiratory and olfactory epithelial tissue. This indicated high potential of the curcumin-HPβCD complex for nose-to-brain delivery of curcumin for treatment of neurodegenerative diseases by means of intranasal administration.Graphical abstract

Silylene-Stabilized Neutral Dibora-Aromatics with a B═B Bond.

The unprecedented silylene-supported dibenzodiboraoxepin 2 and 9,10-diboraphenanthrene complexes 6 and 8 were synthesized. The (NHSi)2B2(xanthene) [NHSi = PhC(NtBu)2(Me2N)Si:] 2 results from debromination of the bis(NHSi)-stabilized bis(dibromoboryl)xanthene 1 with potassium graphite (KC8); 2 is capable of activating white phosphorus and ammonia to form the B2P4 cage compound 3 and H2N-B-B-H diborane species 4, respectively. The thermal rearrangement of 2 affords the 9,10-dihydro-9,10-diboraphenanthrene 5 through a bis(NHSi)-assisted intramolecular reductive C-O-C deoxygenation process. Notably, the 9,10-diboraphenanthrene derivatives 6 and 8 could be generated by deoxygenation of 2 with KC8 and 1,3,4,5-tetramethylimidazol-2-ylidene, respectively. The aromaticity of 6 and 8 was confirmed by computational studies. Strikingly, the NHSi ligand in 8 engenders the monodeoxygenation of carbon dioxide in toluene at room temperature to form the CO-stabilized 9,10-diboraphenanthrene derivative 9 via the silaoxadiborinanone intermediate 10.

Stabilized, ROS-sensitive β-cyclodextrin-grafted hyaluronic supramolecular nanocontainers for CD44-targeted anticancer drug delivery

Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility, biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between β-cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly(ε-caprolactone)-b-poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL-b-PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL-b-PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25 wt% (P1) and 20 wt% (P2) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1-based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1-based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.

Inclusion complex of 2-phenylethanol in β-cyclodextrin: Preparation, characterization, computational study and evaluation of antinociceptive activity

In the present research, we employed advanced technologies, developing new investigations aiming to obtain simple and inexpensive molecules to reduce pain sensation. For the first time, the inclusion complex of 2-phenylethanol (2-PE) and β-cyclodextrin (β-CD) was achieved (using a spray drying) and characterized using spectroscopic, thermal, and computational methods. Additionally, the system was evaluated for its antinociceptive abilities. Evidence of inclusion complex formation was provided based on various techniques, such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR), and then deduced by pharmacological experiments, which showed significant changes compared to the initial components.

Surface modification of carbon dots with cyclodextrins as potential biocompatible photoluminescent delivery/bioimaging nanoplatform

BackgroundCyclodextrins are a well-established system which form inclusion complexes with many guest molecules. This property can be easily exploited to develop drug delivery systems. Additionally, carbon dots (CD) are a low-toxic photoluminescent product which have been used as luminescent tags. The combination of cyclodextrins and carbon dots allows obtaining a new nanoplatform, a biocompatible material, with both capabilities, increasing as well the internalization by the cells of the CD, induced by the cyclodextrins. ResultsIn the present work, we have modified the surface of carbon dots obtained from citric acid and glutathione with β and γ cyclodextrins. After a morphological and spectroscopic characterization, we concluded that the luminescence quantum yield and absorption molar coefficient of the derivatized and unmodified carbon dots was the same. These findings, together with the spectroscopic detection of active cyclodextrins, those bond to the CD able to interact with a guest molecule, allowed determination of the ratios: cyclodextrins/CD, active cyclodextrins/CD and an estimation of the CD molecular mass. Furthermore, the biocompatibility of the new materials was evaluated through cytotoxicity and cell-penetrance assays revealing that the materials were non cytotoxic up to 0.1 mg/mL. Moreover, the biocompatible developed nanoplatform penetrates in the cells maintaining the material's intrinsic fluorescence, thus constituting an adequate photoluminescent-tag with high-contrast for in vitro cell imaging. SignificanceThis work provides a new and easy method to combine cyclodextrins and carbon dots into a biocompatible material which can be used as nanoplatform both as drug delivery system and as photoluminescent tag in cell imaging. Likewise, this paper shows how to characterize the number of cyclodextrins and active cyclodextrins per CD, having an average stoichiometric relation of 1:1 for guest molecule – CD. Additionally, the minimum molecular mass of the unmodified CD was indirectly obtained, yielding about 1.6–1.9 kDa.

Enrofloxacin Pharmaceutical Formulations through the Polymer-Free Electrospinning of β-Cyclodextrin-oligolactide Derivatives.

Enrofloxacin (ENR), a member of the fluoroquinolone class of antibiotics, is widely used in veterinary medicine to treat bacterial infections. Like many antibiotics, ENR has limited water solubility and low bioavailability. To address these challenges, drug formulations using solid dispersions, nanosuspensions, surfactants, cocrystal/salt formation, and inclusion complexes with cyclodextrins may be employed. The approach described herein proposes the development of ENR formulations by co-electrospinning ENR with custom-prepared cyclodextrin-oligolactide (CDLA) derivatives. This method benefits from the high solubility of these derivatives, enabling polymer-free electrospinning. The electrospinning parameters were optimized to incorporate significant amounts of ENR into the CDLA nanofibrous webs, reaching up to 15.6% by weight. The obtained formulations were characterized by FTIR and NMR spectroscopy methods and evaluated for their antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. This study indicates that the presence of CDLA derivative does not inhibit the antibacterial activity of ENR, recommending these formulations for further development.