Β-cyclodextrin Nanoparticles Research Articles

Green Synthesis of Polylactic acid/Fe3O4@β-Cyclodextrin Nanofibrous Nanocomposite Loaded with Ferulago Angulata Extract as a Novel Nano-biosorbent: Evaluation of Diazinon Removal and Antibacterial Activity.

Organophosphate pesticides are one of the most extensively applied insecticides in agriculture. These insecticides persist in the environs and thereby cause severe pollution problems. Iron oxide polymer nanocomposites are wastewater remediation agents synthesized by various methods. When compared to chemical processes, green synthesis using plant extract is thought to be more cost- and environmentally-friendly. This study aimed to evaluate the green synthesis of Fe3O4@β-Cyclodextrin (Fe3O4@β-CD) nanoparticles using Ferulago angulata (F. angulata) methanol extract. These nanoparticles are loaded on polylactic acid (PLA) nanofibrous nanocomposite along with Ferulago angulata extract (2, 4, and, 6wt %) to produce PLA/Fe3O4@β-CD/F. angulata extract nanofibrous nanocomposite as a new nano biosorbent. Furthermore, the antibacterial properties of this compound and its activity in diazinon removal have been evaluated. Fe3O4@β-CD nanoparticles synthesis was performed via co-precipitation method using FeCl3.6H2O and FeCl2.4H2O and β-cyclodextrin, and Ferulago angulata extract. Then polylactic acid/ Fe3O4@β-CD / F. angulate.extract nanofibrous nanocomposite was prepared by the electrospinning method. Energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction analysis (XRD), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR) were used to analyze the structure of the nanocomposite. The antibacterial activity of this nanocomposite against several fish and human bacterial pathogens, as well as its effectiveness in diazinon elimination, have been evaluated in the sections that follow. The nanocomposite structure demonstrated that Fe3O4 nanoparticles were produced and put into the polylactic acid matrix with an average particle size of 40 nm. Furthermore, the results showed that this nanocomposite exhibited removal efficiency of diazinon over 80% after 120 minutes under pH=7 and 2.5 gr.L-1 nanocomposite concentration. Also, this structure showed above 70% antibacterial ability against Bacillus cereus, Staphylococcus epidermidis and 60% antibacterial ability against Streptococcus iniae and Yersinia ruckeri. Fe3O4 nanocomposite synthesis may be accomplished in a delicate and efficient manner by using Ferulago angulata to produce Fe3O4@-CD nanoparticles. The stability of the nanoparticles was enhanced by combining Ferulago angulata extract with polylactic acid nanofibers to create an antibacterial homocomposition nanocomposite. This device may be used to remove and disinfect diazinon from aqueous media in an environmentally friendly manner.

Integrating Synthesis, Physicochemical Characterization, and In Silico Studies of Cordycepin-Loaded Bovine Serum Albumin Nanoparticles.

Cordycepin gets rapidly metabolized in the body into inactive form due to its structural similarity to adenosine, thus inhibiting its development as a medicinal agent. This study was aimed to improve the solubility and stability of cordycepin, a potential drug with known antiproliferative activity, by encapsulating it in bovine serum albumin: β-cyclodextrin nanoparticles. Cordycepin-loaded nanoparticles (CLNPs) were synthesized using the antisolvent method and characterized thoroughly using various techniques. Our dynamic light scattering measurement showed a particle size and zeta potential of 160 ± 2.75 nm and -20.21 ± 2.1 mV, respectively, for CLNPs. Transmission electron microscopy studies revealed that particles were spherical in morphology. These CLNPs showed sustained release of cordycepin with encapsulation and loading efficiency of 81.62 ± 1.5 and 27.02 ± 2.0%, respectively, based on high-performance liquid chromatography and UV-vis studies. Based on differential scanning calorimetry and zeta potential studies, CLNPs improve cordycepin stability and solubility. Our molecular simulations and binding energy calculation also showed favorable protein interaction between cordycepin, bovine serum albumin, and β-cyclodextrin, further supporting the notion of improved stability. In vitro cytotoxicity, apoptosis, and cellular uptake studies on breast cancer cells showed that the synthesized nanoparticles had greater cytotoxicity as compared to free cordycepin.

Green synthesis of dual-spinneret electrospun polyacrylonitrile–ZnO@β-cyclodextrin–chitosan nanofibrous nanocomposite as a novel nano-biosorbent

A significant range of intriguing nanomaterials includes photocatalytic and antibacterial nanocomposites, which exhibit great efficacy in water treatment. In this work, Euphorbia hebecarpa extract was used as a novel natural reducing agent to investigate the environmentally friendly production of ZnO@β-cyclodextrin (CD) nanoparticles (NPs). In the following, polyacrylonitrile, ZnO@β-CD and chitosan nanofibers were electrospun concurrently using a dual-electrospinning process to create a unique nano-biosorbent made of polyacrylonitrile (PAN)–ZnO@β-CD–chitosan (CS) nanofibrous nanocomposite. Additionally, this nanocomposite’s effectiveness as a novel photocatalyst and antibacterial agent for eliminating organic dyes like methylene blue was evaluated. Field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD) analysis, Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy (RS) were used to analyze the structure of the nanocomposite. The outcomes verified the production of ZnO@β-CD, which had evenly shaped particles with an average size of 45 nm on the nanofibrous matrix. This nanocomposite exhibited removal efficiency of methylene blue of ~90% after 105 min at pH 7 and 2.5 g L−1 nanocomposite concentration. Furthermore, an antibacterial test revealed that PAN–ZnO@β-CD–CS nanofibrous nanocomposite with 6% ZnO showed over 80% reduction in colony-forming units per millilitre against Bacillus cereus, Staphylococcus epidermidis and Streptococcus iniae.

Preparation, characterization, and antioxidant activity of β-cyclodextrin nanoparticles loaded Rosa damascena essential oil for application in beverage

Rosa damascena essential oil (REO) is volatile and unstable. The host–guest complex of beta-cyclodextrin nanoparticles (β-CD) with REO was produced to improve REO characteristics. The REO/β-CD complex was characterized by entrapment efficiency, morphology, crystallinity, particle size, thermal stability, and antioxidant activity. Additionally, the structure of REO/β-CD was evaluated using Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR). Results confirmed the formation of REO/β-CD in which the REO, as a guest molecule, was entrapped within the β-CD as a host molecule. The encapsulated particles showed a spherical shape with an average diameter of 110 nm and no strong agglomerate. The entrapment of REO within β-CD led to changes in some physicochemical characteristics and enhancement of the antioxidant activity of REO. Furthermore, beverages with the addition of β-CD nanoparticle-loaded REO were produced. The beverage containing β-CD nanoparticle-loaded REO form showed significantly higher overall acceptability than samples containing free REO.

Tetraethylenepentamine-Coated β Cyclodextrin Nanoparticles for Dual DNA and siRNA Delivery.

Nucleic acid reagents, including plasmid-encoded genes and small interfering RNA (siRNA), are promising tools for validating gene function and for the development of therapeutic agents. Native β-cyclodextrins (BCDs) have limited efficiency in gene delivery due to their instable complexes with nucleic acid. We hypothesized that cationic BCD nanoparticles could be an efficient carrier for both DNA and siRNA. Tetraethylenepentamine-coated β-cyclodextrin (TEPA-BCD) nanoparticles were synthesized, characterized, and evaluated for targeted cell delivery of plasmid DNA and siRNA. The cationic TEPA coating provided ideal zeta potential and effective nucleic acid binding ability. When transfecting plasmid encoding green fluorescent protein (GFP) by TEPA-BCD, excellent GFP expression could be achieved in multiple cell lines. In addition, siRNA transfected by TEPA-BCD suppressed target GFP gene expression. We showed that TEPA-BCD internalization was mediated by energy-dependent endocytosis via both clathrin-dependent and caveolin-dependent endocytic pathways. TEPA-BCD nanoparticles provide an effective means of nucleic acid delivery and can act as potential carriers in future pharmaceutical application.

A Novel Folic Acid Receptor-Targeted Drug Delivery System Based on Curcumin-Loaded β-Cyclodextrin Nanoparticles for Cancer Treatment.

PurposeA novel folate receptor-targeted β-cyclodextrin (β-CD) drug delivery vehicle was constructed to improve the bioavailability, biosafety, and drug loading capacity of curcumin. Controlled release and targeted delivery was achieved by modifying the nanoparticles with folic acid (FA).MethodsFolate-conjugated β-CD-polycaprolactone block copolymers were synthesized and characterized. Curcumin-loaded nanoparticles (FA-Cur-NPs) were structured by self-assembly. The physicochemical properties, stability, release behavior and tumor-targeting ability of the fabricated nanoparticles were studied.ResultsThe average particle size and drug loading of FA-Cur-NPs was 151.8 nm and 20.27%, respectively. Moreover, the FA-Cur-NPs exhibited good stability in vitro for 72 h. The drug release profiles showed that curcumin from FA-Cur-NPs was released significantly faster in a pH 6.4 phosphate buffered solution (PBS) than in pH 7.4, indicating that curcumin can be enriched around the tumor site compared with normal cells. Additionally, the internalization of FA-Cur-NPs was aided by FA receptor-mediated endocytosis, and its cytotoxicity was proportional to the cellular uptake efficiency. Furthermore, in vivo studies confirmed that FA-Cur-NPs exhibited marked accumulation in the tumor site and excellent antitumor activity.ConclusionThese findings suggest that FA-Cur-NPs are a promising approach for improving cancer therapy through active targeting and controllable release.

Antimicrobial photodynamic therapy mediated by methylene blue coupled to β-cyclodextrin reduces early colonizing microorganisms from the oral biofilm

ObjectiveTo test the effect of antimicrobial photodynamic therapy (A-PDT) on the oral biofilm formed with early colonizing microorganisms, using the photosensitizer methylene blue coupled with β-cyclodextrin nanoparticles and red light sources laser or LED (λ =660 nm). MethodsThe groups were divided into (n = 3, in triplicate): C (negative control, 0.9 % NaCl), CX (positive control, 0.2 % chlorhexidine), P (Photosensitizer/Nanoparticle), L (Laser), LED (light-emitting diode), LP (Laser + Photosensitizer/Nanoparticle) and LEDP (LED + Photosensitizer/Nanoparticle). A multispecies biofilm composed ofS. gordonii, S. oralis, S. mitis, and S. sanguinis was grown in microplates containing BHI supplemented with 1% sucrose (w/v) for 24 h. Light irradiations were applied with a laser at 9 J for 90 s (320 J/cm2), or with LED, at 8.1 J for 90 s (8.1 J/cm2). The microbial reduction was assessed by counting viable biofilm microorganisms in selective culture media, before and after the treatments. Data normality was assessed by the Shapiro-Wilk test, and the results were submitted to Kruskal-Wallis analysis, followed by Dunn's test, with a significance level of 5%. ResultsThe groups LP and LEDP were able to significantly reduce the biofilm microorganism counts by as much as 4 log10 times compared to the negative control group (p < 0.05) and did not statistically differ from the positive control group (CX) (p > 0.05). ConclusionThe A-PDT mediated by encapsulated β-cyclodextrin methylene blue irradiated by Laser or LED was effective in the microbial reduction of multispecies biofilm composed of early colonizing microorganisms.

Partial inclusion complex assisted crosslinked β-cyclodextrin nanoparticles for improving therapeutic potential of docetaxel against breast cancer.

The present investigation demonstrates the development of crosslinked β-cyclodextrin nanoparticles (β-CD NPs) for enhancing the therapeutic efficacy of docetaxel (DTX) against breast cancer. Initially, a partial inclusion complex between β-CD and polypropylene glycol (PPG) was formed to induce self-assembly. This was followed by crosslinking of β-CDs using epichlorohydrin (EPI) and removal (by solubilization) of PPG to yield uniform β-CD NPs. The formed particles were used for loading DTX to form DTX β-CD NPs. The resultant DTX β-CD NPs exhibited particle size of 223.36 ± 17.73nm with polydispersity index (PDI) of 0.13 ± 0.09 and showed entrapment efficiency of 54.53 ± 2%. Increased cell uptake (~5-fold), cytotoxicity (~3.3-fold), and apoptosis were observed in MDA-MB-231 cells when treated with DTX β-CD NPs in comparison to free DTX. Moreover, pharmacokinetic evaluation of DTX β-CD NPs revealed ~2 and ~5-fold increase in AUC0-∞ and mean residence time (MRT) of DTX when compared to Docepar®. Further, the anti-tumor activity using DMBA-induced cancer model showed that DTX β-CD NPs were capable of reducing the tumor volume to ~40%, whereas Docepar® was able to reduce tumor volume till ~80%. Finally, the toxicity evaluation of DTX β-CD NPs revealed no short-term nephrotoxicity and was confirmed by estimating the levels of biomarkers and histopathology of the organs. Thus, the proposed formulation strategy can yield uniformly formed β-CD NPs which can be effectively utilized for improving the therapeutic efficacy of DTX.

Magnetic Ti3C2 MXene functionalized with β-cyclodextrin as magnetic solid-phase extraction and in situ derivatization for determining 12 phytohormones in oilseeds by ultra-performance liquid chromatography-tandem mass spectrometry

Magnetic solid phase extraction integrated with in situ derivations for the profiling of 12 phytohormones in a single rapeseed seed was developed by using ultra-high performance liquid chromatography-tandem mass spectrometry. The Fe3O4@Ti3C2@β-cyclodextrin nanoparticles were firstly synthesized and used as an adsorbent for the solid-phase extraction of phytohormones. The magnetic dispersive solid-phase extraction and in situ derivation by the addition of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide were ingeniously combined. This efficient pre-treatment method integrated the extraction, purification, and derivatization processes into one single step. Satisfactory methodological performance was achieved by optimization of the parameters. Linearities (R2 > 0.9928) and recoveries (80.4 %–115.1%) at three spiked levels, as well as the low matrix effect (from −16.63% to 17.06%) and limits of detection (0.89–13.62 pg/mL) were obtained. The spatio-temporal profiling of target phytohormones in different tissues of rapeseed germination was investigated. This method was successfully employed for analyzing target phytohormones in different oilseeds samples.

Co3O4@β-cyclodextrin with synergistic peroxidase-mimicking performance as a signal magnification approach for colorimetric determination of ascorbic acid

Transition metal oxides nanoparticles have shown enzyme-mimetic performance. It was demonstrated that the Co3O4@β-cyclodextrin nanoparticles (Co3O4@β-CD NPs) showed a higher peroxidase-mimicking catalytic activity than pure Co3O4 NPs. β-CD molecules were coated onto the surface of Co3O4 NPs via a one-pot synthesis method. Co3O4@β-CD NPs displayed higher affinity to 3,3′,5,5′-tetramethylbenzidine (TMB) through Michaelis-Menten mechanism after modification with β-CD. The catalytic efficiency of Co3O4@β-CD NPs for TMB oxidation was 9.5-fold higher than that of the pure Co3O4 NPs because of the effective host-guest interactions between Co3O4@β-CD NPs and TMB. Further, the hydrophobic cavity of β-CD while hosting TMB could reduce the transfer distance of electrons between TMB and Co3O4 catalyst, which could lead to faster oxidation of TMB. The synergistic effects between Co3O4 and β-CD enhanced the peroxidase-mimicking property. The efficient and visual colorimetric determination of Ascorbic Acid (AA) assay was achieved. The limit of detection was 1.09 μM (S/N = 3) and the linear range was 10–60 μM based on the Co3O4@β-CD NPs peroxidase-mimicking-mediated 3.0-fold signal magnification strategy. Moreover, the outstanding selectivity toward the detection of AA was achieved, which could exhibit prospects in biomedical analysis.

Combined Effectiveness of β-Cyclodextrin Nanoparticles in Photodynamic Antimicrobial Chemotherapy on In Vitro Oral Biofilms.

Objective: This study aimed to investigate if β-cyclodextrin nanoparticles potentiate the photodynamic antimicrobial chemotherapy (PACT) effects in single and microcosm oral biofilms using methylene blue (MB) and a red laser. Background data: Studies of PACT have demonstrated promising effects; however, the association of nanoparticles with photosensitizers could enhance the antimicrobial result. Materials and methods: Biofilms were grown on enamel blocks either with Streptococcus mutans or in a microcosm model (salivary microorganisms) supplemented with sucrose. PACT using 50 μM MB associated or not with 32 μM encapsulated β-cyclodextrin with MB for 5 min, followed by irradiation with red laser (λ = 660 nm, 320 J/cm2), was conducted and the counts of viable microorganisms in proper selective media were determined. Data were analyzed by one-factor ANOVA, followed by Tukey's test, or Kruskal-Wallis test, followed by Dunn's post hoc test, all with a significance level of 5%. Results: In the single-species biofilm model, a significant reduction in S. mutans counts was found for all groups when light was present. In the microcosm biofilm model, no significant difference was found among the groups for total streptococci, but a significant reduction of S. mutans was observed for the PACT group of encapsulated β-cyclodextrin+MB. However, no statistically significant difference was observed among the PACT groups. Conclusions: PACT with β-cyclodextrin mediated with MB associated with a red laser reduced S. mutans in microcosm biofilms. However, the presence of β-cyclodextrin nanoparticles did not potentiate the PACT effects in single or microcosm oral biofilms.

Fabrication and evaluation of novel quercetin-conjugated Fe3O4-β-cyclodextrin nanoparticles for potential use in epilepsy disorder.

BackgroundDespite the numerous pharmacological activities of quercetin, its biomedical application has been hampered, because of poor water solubility and low oral bioavailability. In the present study, we fabricated a novel form of quercetin-conjugated Fe3O4–β-cyclodextrin (βCD) nanoparticles (NPs), and the effect of these prepared NPs was evaluated in a chronic model of epilepsy.MethodsQuercetin-loaded NPs were prepared using an iron oxide core coated with βCD and pluronic F68 polymer. The chronic model of epilepsy was developed by intraperitoneal injection of pentylenetetrazole (PTZ) at dose of 36.5 mg/kg every second day. Quercetin or its nanoformulation at doses of 25 or 50 mg/kg were administered intraperitoneally 10 days before PTZ injections and their applications continued 1 hour before each PTZ injection. Immunostaining was performed to evaluate the neuronal density and astrocyte activation of hippocampi.ResultsOur data showed successful fabrication of quercetin onto Fe3O4–βCD NPs. In comparison to free quercetin, quercetin NPs markedly reduced seizure behavior, neuronal loss, and astrocyte activation in a PTZ-induced kindling model.ConclusionOverall, quercetin–Fe3O4–βCD NPs might be regarded as an ideal therapeutic approach in epilepsy disorder.

HS-β-cyclodextrin-functionalized Ag@Fe3O4@Ag nanoparticles as a surface-enhanced Raman spectroscopy substrate for the sensitive detection of butyl benzyl phthalate.

In recent years, there have been incidents involving the illegal addition of phthalic acid esters (PAEs) to liquors. It is well known that PAEs such as butyl benzyl phthalate (BBP) have estrogen-like effects, so high PAE levels in the body can lead to a decreased sperm count in males and altered sexual organ development in children, for example. The rapid detection of PAEs in liquor is therefore an important task. Compared with traditional methods of testing for PAEs, surface-enhanced Raman spectroscopy (SERS) offers higher sensitivity and the ability to search for chemical fingerprints, allowing the rapid detection of particular PAEs. In the present work, we synthesized Ag@Fe3O4@Ag/β-cyclodextrin (CD) nanoparticles for use as a SERS-active substrate. Fe3O4 aggregates quickly under the influence of an external magnetic field, making it possible to magnetically separate out the NPs, which simplifies sample processing. The detection limit of the system for PAEs is also improved because the β-CD acts as a functional group with a cavity structure that is capable of adsorbing BBP to form a host (β-CD)-guest (BBP) complex. This substrate was shown to possess good repeatability and sensitivity when using malachite green (MG) as a probe molecule. Furthermore, the nanoparticle-based SERS substrate permitted the detection of BBP down to a level of 1.3mg/kg in liquor, which is low enough to be able to detect BBP in real-world liquor samples. We expect that this method will prove useful for the rapid detection of PAEs in food. Graphical abstract.

Folic acid-modified β-cyclodextrin nanoparticles as drug delivery to load DOX for liver cancer therapeutics

ABSTRACTTo get the safe and effective therapy for liver cancer, multifunctional nanoparticulate systems with therapeutic efficacy for biomedical application are progressing quite rapidly. The aim of the present research is to determine the potential of doxorubicin (DOX)-loaded folic acid–polyethylene glycol–β-cyclodextrin (FA–PEG–β-CD) nanoparticles (NPs) as drug-delivery system for liver cancer therapy. The targeting delivery of FA–PEG–β-CD was synthesized from FA and β-CD with PEG as a linker, which then loaded antitumor drug DOX to get the FA–PEG–β-CD/DOX NPs. The physicochemical characterizations including flourier transform infrared, 1H nuclear magnetic resonance, transmission electron microscope and dynamic light scattering, drug-loading content, drug encapsulation efficiency, blood compatibility, and in-vitro drug release were investigated. Finally, the in-vitro antitumor activity was estimated by HepG2 cells. The size of FA–PEG–β-CD NPs was about 20–80 nm, while FA–PEG–β-CD/DOX NPs was 30–60 nm. And the FA–PEG–β-CD/DOX NPs have drug-loading efficiency (11.9%) and encapsulation efficiency (95.2%). The in-vitro drug release results showed that the FA–PEG–β-CD NPs could not merely improve the solubility of hydrophobic drugs but also control the drug release. Blood compatibility assays revealed that DOX-loaded NPs did not induce blood hemolysis. In summary, the drug delivery of FA–PEG–β-CD NPs is suitable to carry the drug to the tumor tissues and release the drug effectively, and FA–PEG–β-CD/DOX NPs may be a potential platform for improving the treatment of liver cancer.

The redox mechanism investigation of non-small cell lung cancer drug: Erlotinib via theoretical and experimental techniques and its host–guest detection by β-Cyclodextrin nanoparticles modified glassy carbon electrode

Erlotinib (ERL) is a tyrosine kinase inhibitor which prevents growing of cancer cells. The electrochemical oxidation mechanism of ERL was studied in details using cyclic voltammetry. Cyclic voltammetry, differential pulse and square wave voltammetric techniques were applied for sensitive, fast, precise determination of ERL. Adsorptive stripping square wave voltammetry was selected and applied to the assay of ERL in pharmaceutical dosage forms. Quantitative application and its validation were realized via β-Cyclodextrin nanoparticles modified glassy carbon electrode in 0.1 M phosphate buffer pH 3.0 in the presence of 20% methanol. The adsorptive stripping square wave voltammetry provided linear response within the concentration ranges 1.00 × 10−8 M - 8.00 × 10-6 M (r = 0.999) with LOD and LOQ values 1.07 × 10-9 M and 3.58 × 10-9 M, respectively. The recovery of erlotinib in Tarceva® tablets was 100.38%. In addition, computational studies were exerted to complement to the analytical studies, The molecular electrostatic potential surface and frontier molecular orbitals have been calculated at the DFT level and on B3LYP/6‑31+G* to elucidate the ERL oxidation behavior. The results shown that the theoretical data were consistent with the proposed oxidation mechanism of ERL.

The promotion of tissue engineering blood vessel patency by CGS21680 through regulating pro-inflammatory activities of endothelial progenitor cell.

The mobilization and homing of endothelial progenitor cells (EPCs) contribute to the rapid endothelialization of tissue engineering blood vessel (TEBV). Inflammation can affect TEBV patency, and monocytes/macrophages (MM) are the main effector cells. But it is not clear how EPCs interact with MM after TEBV transplantation. Our results showed acellular materials would not directly cause acute and severe inflammatory responses but activate E-selectin expression in homing EPCs, gradually promoting the polarization of MM to the M1. Adenosine A2a receptor agonist CGS21680 promoted the secretion of more proangiogenic factors from MM, inducing EPC migration and mobilization. CGS21680 could inhibit MM polarization to the M1 type through the down-regulation of EPC proinflammatory molecules, such as E-selectin. Chitosan/(2-hydroxypropyl)-β-cyclodextrin nanoparticles were prepared to control the release of CGS-21680 and then modified to TEBVs through layer-by-layer assembly. Animal experiments showed that this TEBV can maintain patency for 6 months and good endothelialization was observed. In summary, our results showed the regulation of EPC pro-inflammatory activities is a new approach to enhance TEBV patency. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2634-2642, 2018.

TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy.

Tumour-associated macrophages (TAMs) are abundant in many cancers, and often display an immune-suppressive M2-like phenotype that fosters tumour growth and promotes resistance to therapy. Yet macrophages are highly plastic and can also acquire an anti-tumourigenic M1-like phenotype. Here, we show that R848, an agonist of the toll-like receptors (TLRs) TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro and that R848-loaded β-cyclodextrin nanoparticles (CDNPs) lead to efficient drug delivery to TAMs in vivo. As a monotherapy, the administration of CDNP-R848 in multiple tumour models in mice altered the functional orientation of the tumour immune microenvironment towards an M1 phenotype, leading to controlled tumour growth and protecting the animals against tumour rechallenge. When used in combination with the immune checkpoint inhibitor anti-PD-1, we observed improved immunotherapy response rates, also in a tumour model resistant to anti-PD-1 therapy. Our findings demonstrate the ability of rationally engineered drug–nanoparticle combinations to efficiently modulate TAMs for cancer immunotherapy.

The Effect of Molecular Architecture of Sulfobutyl Ether β-Cyclodextrin Nanoparticles on Physicochemical Properties of Complexes with Moxifloxacin

A method has been developed for nanoparticles synthesis based on oligomers of sulfobutyl ether β-cyclodextrin (SBE-β-CD) and their structure has been studied by FTIR spectroscopy. The physicochemical properties of “guest−host” inclusion complexes formed by SBE-β-CD and its oligomers with moxifloxacin have been investigated. It has been shown that, as compared with SBE-β-CD, the synthesized oligomers have an increased affinity for moxifloxacin: the dissociation constants for the complexes of monomeric and oligomeric SBE-β-CD are (1.0 ± 0.3) × 10−4 and nearly 5 × 10−6 M, respectively. The binding efficiency increases due to the multy-point interaction of a moxifloxacin molecule with functional groups of the oligomeric carrier. SBE-β-CD oligomers are promising carriers for drugs, in particular, fluoroquinolone-based antibacterial agents, and may be used for the development of new compositions with improved solubility, bioavailability, and prolonged drug release.

Preparation and Characterization of Nanoparticle β-Cyclodextrin:Geraniol Inclusion Complexes.

The aim of the present study was to formulate β-cyclodextrin (β-CD) nanoparticles loaded with geraniol (GR) essential oil (EO) with appropriate physicochemical properties. Complexation of GR with β-CD was optimized by evaluation of four formulations, using the co-precipitation method, and the encapsulation efficiency (EE), loading, size, particle size distribution (PDI) and zeta potential were investigated. Further characterization was performed with nuclear magnetic resonance spectroscopy (1H NMR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and infra-red (IR) spectroscopy analysis. Results showed that the physicochemical properties of the nanoparticles were affected by GR content in formulations that yielded nanoscale-size particles ranging from 111 to 258 nm. The highest encapsulation efficiency (79.4 ± 5.4%) was obtained when the molar ratio of EO to β-CD was 0.44: 0.13 with negative zeta potential (-21.1 ± 0.5 mV). The 1H-NMR spectrum confirmed the formation structure of the EO and β-CD nanoparticle complex. Complexation with geraniol resulted in changes of IR profile, NMR chemical shifts, DSC properties, and SEM of β-cyclodextrin. Inclusion complex of essential oil with β-cyclodextrin was considered as promising bioactive materials for designing functional food.

Biocompatible crosslinked β-cyclodextrin nanoparticles as multifunctional carriers for cellular delivery.

Nanoparticle-based biomedicine has received enormous attention for theranostic applications, as these systems are expected to overcome several drawbacks of conventional therapy. Herein, effective and controlled drug delivery systems with on-demand release abilities and biocompatible properties are used as a versatile and powerful class of nanocarriers. We report the synthesis of a novel biocompatible and multifunctional material, entirely consisting of covalently crosslinked organic molecules. Specifically, β-cyclodextrin (CD) precursors were crosslinked with rigid organic linker molecules to obtain small (∼150 nm), thermally stable and highly water-dispersible nanoparticles with an accessible pore system containing β-CD rings. The nanoparticles can be covalently labeled with dye molecules to allow effective tracking in in vitro cell experiments. Rapid sugar-mediated cell-uptake kinetics were observed with HeLa cells, revealing exceptional particle uptake within only 30 minutes. Additionally, the particles could be loaded with different cargo molecules showing pH-responsive release behavior. Successful nuclei staining with Hoechst 33342 dye and effective cell killing with doxorubicin cargo molecules were demonstrated in live-cell experiments, respectively. This novel nanocarrier concept provides a promising platform for the development of controllable and highly biocompatible theranostic systems.