betadex and benzimidazole

To enhance drug utilization and reduce their side effects, the strategy of "tumor-triggered targeting" was introduced to fabricate dual-pH-sensitive chitosan (CHI)/mesoporous silica nanoparticle (MSN)-based anticancer drug delivery system (DDS) in this work. Model drug doxorubicin hydrochloride (DOX) was loaded in MSN, which was modified with benzimidazole (Bz) group. Then chitosan-graft-β-cyclodextrin (CHI-g-CD) was applied as the "gatekeeper" to cover MSN through host-guest interaction between β-CD and Bz. After being coated with targeting peptide adamantane-glycine-arginine-glycine-aspartic acid-serine (Ad-GRGDS), methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) was finally grafted on CHI through the pH-sensitive benzoic imine bond. Due to the dynamic protection of PEG, the obtained carriers were "stealthy" at pH 7.4, but could reveal the shielded targeting peptide and the positive charge of CHI in the weakly acidic environment achieved a "tumor-triggered targeting". Inside cancer cells, the interaction between β-CD and Bz group could be destroyed due to the lower pH, resulted in DOX release. Both in vitro and in vivo studies proved the DDS could targeting induce cancer cell apoptosis, inhibit tumor growth, and reduce the cytotoxicity of DOX against normal cells. It is expected that the system named DOX@MSN-CHI-RGD-PEG could be a potential choice for cancer therapy.

Topics: Adamantane; Animals; Antibiotics, Antineoplastic; Benzimidazoles; beta-Cyclodextrins; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Chitosan; Delayed-Action Preparations; Doxorubicin; Drug Carriers; Drug Compounding; Female; Hydrogen-Ion Concentration; Mice; Mice, Inbred BALB C; Nanoparticles; Oligopeptides; Polyethylene Glycols; Porosity; Silicates; Tumor Burden

Topics: Animals; Antineoplastic Agents; Benzimidazoles; beta-Cyclodextrins; Cell Line, Tumor; Cell Movement; Cell Survival; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Female; Ferrous Compounds; Heparin, Low-Molecular-Weight; Hydrogen-Ion Concentration; Metallocenes; Mice, Inbred BALB C; Nanoparticles; Neoplasm Invasiveness; Pentacyclic Triterpenes; Polyethyleneimine; Polylactic Acid-Polyglycolic Acid Copolymer; Reactive Oxygen Species; Stimuli Responsive Polymers; Triple Negative Breast Neoplasms; Tumor Burden

The design of pH-sensitive supramolecular drug delivery systems for efficient antineoplastic drug delivery remains a huge challenge. Herein, we describe the development of pH-responsive core-shell tecto dendrimers (CSTDs) formed using benzimidazole (BM)-modified generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers (G3.NHAc-BM) as a shell and β-cyclodextrin (CD)-modified G5 PAMAM dendrimers (G5.NHAc-CD) as a core. By virtue of the host-guest recognition and pH-responsiveness of BM/β-CD assembly, the pH-sensitive supramolecular CSTDs of G5.NHAc-CD/BM-G3.NHAc were formed and adopted to encapsulate the anticancer drug doxorubicin (DOX) via hydrophobic interactions for pH-responsive drug delivery applications. The synthesis of dendrimer derivatives and the loading of the DOX were well characterized via different methods. We show that the encapsulated DOX can be released in a sustained manner with a rapid release speed under a slightly acidic pH condition (pH < 6), which is similar to acidic tumor microenvironment. The enhanced intracellular release of DOX and improved anticancer activity of the drug-loaded pH-responsive CSTDs were demonstrated and compared with the control CSTDs formed without pH-responsiveness through flow cytometry and viability assays of cancer cells. Furthermore, the pH-sensitive CSTDs also showed efficient drug penetration and growth inhibition of three-dimensional tumor spheroids owing to the faster DOX release in an acidic pH environment. The pH-sensitive G5.NHAc-CD/BM-G3.NHAc CSTDs may be employed as a valuable intelligent delivery system for various anticancer drugs.

Topics: Antineoplastic Agents; Benzimidazoles; beta-Cyclodextrins; Cell Survival; Dendrimers; Doxorubicin; Drug Carriers; Drug Liberation; HeLa Cells; Humans; Hydrogen-Ion Concentration

In this paper, temperature and pH dual-sensitive supramolecular micelles were constructed from star polymer β-cyclodextrin-poly(N-isopropylacrylamide) (β-CD-PNIPAM) and benzimidazole terminated poly(ε-caprolactone) (BM-PCL). The supramolecular micelles were formed based on the reversible host-guest recognition between β-CD and BM. The size of supramolecular micelles was about 50-100 nm and the LCST was about 30.5 ℃. The drug loading efficiency of supramolecular micelles for DOX was high due to the hydrophobic micelles core of PCL and hydrophobic cavity of β-CD. The release of drugs from supramolecular micelles was suppressed at neutral solution and room temperature but accelerated at acidic solution and 37 ℃. The drug loaded supramolecular micelles exhibited higher anti-cancer activity than free drugs. These temperature and pH dual-sensitive supramolecular micelles might possess potential applications for anticancer drug delivery.

Topics: Acrylic Resins; Benzimidazoles; beta-Cyclodextrins; Cell Death; Doxorubicin; Drug Delivery Systems; HeLa Cells; Humans; Hydrodynamics; Hydrogen-Ion Concentration; Micelles; Particle Size; Polyesters; Proton Magnetic Resonance Spectroscopy; Spectroscopy, Fourier Transform Infrared; Static Electricity; Temperature

This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular β-cyclodextrin:benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies.

Topics: Acetylcholine; Acetylcholinesterase; Benzimidazoles; beta-Cyclodextrins; Cell Survival; Doxorubicin; Drug Carriers; Enzymes, Immobilized; Gold; HeLa Cells; Humans; Hydrogen-Ion Concentration; Hydrolysis; Nanoparticles; Organometallic Compounds; Porosity; Silicon Dioxide

A novel controlled release system-based sandwich-type immunosensor is fabricated to detect squamous cell carcinoma antigen (SCCA). The 1-methyl-1H-benzimidazole functionalized mesoporous SiO2 (MBI-MS) is used to load methylene blue (MB). β-cyclodextrin functionalized gold (CD-Au) is introduced as the gatekeeper for encapsulating MB and capturing the adamantly functional detection antibody (ADA-Ab2). And pH stimulus serves as the trigger system to control the MB release. After the load of MB, the CD-Au blocks the pores of the MBI-MS by the host-guest interaction in the neutral condition. However, when the pH is below 7.0, CD-Au is separated from the surface of MBI-MS owing to the protonation of the aromatic amines. The encapsulated MB is released from the pores of MBI-MS and detected by square wave voltammetry. The controlled release immunosensor shows a relatively wide linear range from 0.001 to 20 ng · mL(-1) with a low detection limit of 0.25 pg · mL(-1). The immunosensor also shows good reproducibility and selectivity, which endows it broad application prospect in clinical research.

Topics: Benzimidazoles; beta-Cyclodextrins; Biosensing Techniques; Delayed-Action Preparations; Dielectric Spectroscopy; Gold; Hydrogen-Ion Concentration; Porosity; Reproducibility of Results; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared

Herein, learning from the idea of the modular concept widely used in ship building, as a design approach that assembles some subdivided smaller modules to a specific ship, a new modular multifunctional drug delivery (MMDD) with excellent biocompatibility was directly prepared by a flexible host-guest interaction between pH-sensitive benzimidazole-graft-dextran (Dex-BM) and pre-synthesized multifunctional cyclodextrins. In this drug system, pH-sensitive Dex-BM acted as the main case and pre-synthesized multifunctional cyclodextrins were the changeable modules. To verify the feasibility of MMDD in cancer chemotherapy, doxorubicin (DOX) was used as a model drug. In vitro drug release experiments indicated that the drug released around 80% from DOX-loaded MMDD at pH 5.3, while approximately 40% of DOX released under the condition of pH 7.4. Moreover, the targeting antitumor activity of DOX-loaded MMDD was investigated in HeLa and HepG2 cells using MTT assays, confocal laser scanning microscopy and flow cytometer, which indicated that the targeted DOX-loaded MMDD provided an efficient drug delivery platform for inhibition of different cancer cells. Meantime, the incorporation of different functional modules into one system was also investigated, simultaneously exhibiting targeting and imaging property. These features suggest that this modular multifunctional drug delivery system can efficiently enhance the inhibition of cellular proliferation in vitro, and according to the needs in clinical treatment, some targeting and imaging molecules can be chosen.

Topics: Antineoplastic Agents; Benzimidazoles; beta-Cyclodextrins; Cell Death; Cell Proliferation; Dextrans; Disaccharides; Doxorubicin; Drug Delivery Systems; Drug Liberation; Flow Cytometry; Fluorescein-5-isothiocyanate; Folic Acid; HeLa Cells; Hep G2 Cells; Humans; Intracellular Space; Micelles; Proton Magnetic Resonance Spectroscopy; Spectrometry, Fluorescence

pH-responsive supramolecular amphiphilic micelles based on benzimidazole-terminated poly(ethylene glycol) (PEG-BM) and β-cyclodextrin-modified poly(L-lactide) (CD-PLLA) were developed by exploiting the host-guest interaction between benzimidazole (BM) and β-cyclodextrin (β-CD). The dissociation of the supramolecular micelles was triggered in acidic environments. An antineoplastic drug, doxorubicin (DOX), was loaded into the supramolecular micelles as a model drug. The release of DOX from the supramolecular micelles was clearly accelerated as the pH was reduced from 7.4 to 5.5. The DOX-loaded PEG-BM/CD-PLLA supramolecular micelles displayed an enhanced intracellular drug-release rate in HepG2 cells compared to the pH-insensitive DOX-loaded PEG-b-PLLA counterpart. After intravenous injection into nude mice bearing HepG2 xenografts by the tail vein, the DOX-loaded supramolecular micelles exhibited significantly higher tumor inhibition efficacy and reduced systemic toxicity compared to free DOX. Furthermore, the DOX-loaded supramolecular micelles showed a blood clearance rate markedly lower than that of free DOX and comparable to that of the DOX-loaded PEG-b-PLLA micelles after intravenous injection into rats. Therefore, the pH-responsive PEG-BM/CD-PLLA supramolecular micelles hold potential as a smart nanocarrier for anticancer drug delivery.

Topics: Antineoplastic Agents; Benzimidazoles; beta-Cyclodextrins; Cell Death; Doxorubicin; Drug Delivery Systems; Flow Cytometry; HeLa Cells; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Lactates; Micelles; Polyethylene Glycols; Pyrenes; Spectrometry, Fluorescence

In this study, lansoprazole (LSP)/cyclodextrin (CD) inclusion complexes were prepared using a fluid bed coating technique, with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HPCD) as the host molecules, respectively, to simultaneously improve the dissolution and stability of LSP. The dissolution rate and stability of LSP was dramatically enhanced by inclusion complexation regardless of CD type. LSP/HPCD inclusion complex was more stable under illumination than LSP/β-CD inclusion complex. Differential scanning calorimetry and powder X-ray diffractometry proved the absence of crystallinity in both LSP/CD inclusion complexes. Fourier transform infrared spectroscopy together with molecular modeling indicated that the benzimidazole of LSP was included in the cavity of both CDs, while LSP was more deeply included in HPCD than β-CD. The enhanced photostability was due to the inclusion of the sulfinyl moiety into the HPCD cavity. CD inclusion complexation could improve the dissolution and stability of LSP.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; 2-Pyridinylmethylsulfinylbenzimidazoles; Benzimidazoles; beta-Cyclodextrins; Calorimetry, Differential Scanning; Drug Stability; Lansoprazole; Models, Molecular; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction