Preparation of β-CD-DPPE-Dox Nanomedicine and Its’ Application as the Anticancer and Antitumor Drug

Abstract β-CD-DPPE molecule was synthesized through the conjugation of β-CD-NH2 and the DPPE molecule, and its’ water-solubility was more excellent than the traditional phospholipid molecule. The spherical micelles was formed by β-CD-DPPE molecule in aqueous solution, and the β-CD-DPPE-Dox nanomedicine can be prepared through loading Dox (Doxorubicin) into the micelles, and the Dox loading ratio was about 82.3 ± 7.27%. At the same time the Dox release behavior from the nanomedicine was sustained-release and pH controlled release, and the release test in vitro showed that the release rate of the Dox at the lower pH was faster than that of normal pH (pH = 7.4), which indicated that the rate of release in the tumor microenvironment is faster than in the normal tissue. Biological test showed that the micelles was low cytotoxicity, and the cytotoxicity of β-CD-DPPE-Dox nanomedicine was lower than the Dox under the same Dox concentration, and the β-CD-DPPE-Dox nanomedicine could effectively induce cancer cell apoptosis and inhibit the tumor growth.

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Non-cytotoxic hydroxyl-functionalized exfoliated boron nitride nanoflakes impair the immunological function of insect haemocytes in vivo

Scientific Reports ◽

10.1038/s41598-019-50097-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Elżbieta Czarniewska ◽

Lucyna Mrówczyńska ◽

Magdalena Jędrzejczak-Silicka ◽

Patryk Nowicki ◽

Martyna Trukawka ◽

...

Keyword(s):

Boron Nitride ◽

Water Solubility ◽

Hexagonal Boron Nitride ◽

Hydroxyl Groups ◽

Latex Beads ◽

Insect Haemocytes ◽

Low Cytotoxicity

Abstract To induce the water solubility of hexagonal boron nitride (h-BN), we exfoliated and functionalized bulk h-BN with hydroxyl groups (h-BN-OH-n). Short-term studies showed that h-BN-OH-n induced low cytotoxicity in different models: insect haemocytes (in vivo), human erythrocytes and mouse fibroblasts (in vitro). We also demonstrated that Alexa Fluor 647-h-BN-OH-n administered topically to the insects passed through the cuticle barrier and was phagocytosed by haemocytes. Nanoflakes did not affect the haemocyte cell membrane and did not interfere with the phagocytosis of latex beads. Long-term immunoassays showed that h-BN-OH-n, despite not inducing haemocytotoxicity, impaired nodulation, the most important cellular immune response in insects. The haemocytes exposed to h-BN-OH-n and then to bacteria differed in morphology and adhesiveness from the haemocytes exposed only to bacteria and exhibited the same morphology and adhesiveness as the control haemocytes. The h-BN-OH-n-induced decrease in nodulation can therefore result from the reduced ability of haemocytes to recognize bacteria, migrate to them or form microaggregates around them, which can lead to dysfunction of the immune system during pathogen infection. Long-term in vivo studies with animal models are still necessary to unambiguously confirm that h-BN is biocompatible and useful for application as a platform for drug delivery or for bioimaging.

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Facile Synthesis of Holmium-Based Nanoparticles as a CT and MRI Dual-Modal Imaging for Cancer Diagnosis

Frontiers in Oncology ◽

10.3389/fonc.2021.741383 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tianqi Zhang ◽

Mo Deng ◽

Lei Zhang ◽

Zerun Liu ◽

Yang Liu ◽

...

Keyword(s):

Water Solubility ◽

Rapid Development ◽

Modern Medicine ◽

Cancer Diagnostics ◽

Mri Imaging ◽

X Ray ◽

Low Cytotoxicity ◽

Magnetic Resonance Imaging Mri ◽

Intensive Investigation

The rapid development of medical imaging has boosted the abilities of modern medicine. As single modality imaging limits complex cancer diagnostics, dual-modal imaging has come into the spotlight in clinical settings. The rare earth element Holmium (Ho) has intrinsic paramagnetism and great X-ray attenuation due to its high atomic number. These features endow Ho with good potential to be a nanoprobe in combined x-ray computed tomography (CT) and T2-weighted magnetic resonance imaging (MRI). Herein, we present a facile strategy for preparing HoF3 nanoparticles (HoF3 NPs) with modification by PEG 4000. The functional PEG-HoF3 NPs have good water solubility, low cytotoxicity, and biocompatibility as a dual-modal contrast agent. Currently, there is limited systematic and intensive investigation of Ho-based nanomaterials for dual-modal imaging. Our PEG-HoF3 NPs provide a new direction to realize in vitro and vivo CT/MRI imaging, as well as validation of Ho-based nanomaterials will verify their potential for biomedical applications.

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Evaluation of the Release Behavior of the Dexamethasone Embedded in Polycarbonate Polyurethane Membranes: An In Vitro Study

Journal of the Korean Radiological Society ◽

10.3348/jkrs.2003.48.1.7 ◽

2003 ◽

Vol 48 (1) ◽

pp. 7 ◽

Cited By ~ 3

Author(s):

Dong Hyun Kim ◽

Sung Gwon Kang ◽

Sang Soo Park ◽

Don Haeng Lee ◽

Gyu Baek Lee ◽

...

Keyword(s):

In Vitro Study ◽

Vitro Study ◽

Release Behavior ◽

Polyurethane Membranes

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Complexation with Hydroxypropyl-gama-Cyclodextrin of Birch Tree Extract Physico-chemical Characterisation of their Binary Products

Revista de Chimie ◽

10.37358/rc.08.6.1854 ◽

2008 ◽

Vol 59 (6) ◽

Cited By ~ 1

Author(s):

Codruta Soica ◽

Cristina A. Dehelean ◽

Valentin Ordodi ◽

Diana Antal ◽

Vicentiu Vlaia

Keyword(s):

Inclusion Complexes ◽

Water Solubility ◽

In Vitro Dissolution ◽

Molar Ratio ◽

Bark Extract ◽

Birch Bark ◽

Preparation Methods ◽

Birch Tree ◽

Physico Chemical

Birch bark contains important pentacyclic triterpens that determine an anticancer, anti-inflammatory and antiviral activity. The compounds can be extracted by simple procedures with organic solvents. The major problem of this type of triterpens is their low water solubility which can be increased by physical procedures like cyclodextrin complexation. The aim of present study was to analyse the products between birch bark extract and hydroxypropyl-g -cyclodextrin. Hydroxypropyl-g -cyclodextrin (HPGCD) was used as a host to improve its solubility in water, via inclusion complex formation. In order to obtain the inclusion complexes, 1:2 molar ratio and two preparation methods (physical mixing, kneading) were used. The inclusion complexes were analyzed by in vitro dissolution tests, thermal analysis and X-ray diffraction.

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Targeting Breast Cancer Cells with G4 PAMAM Dendrimers and Valproic Acid Derivative Complexes

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200423073812 ◽

2020 ◽

Vol 20 (15) ◽

pp. 1857-1872

Author(s):

Alberto M. Muñoz ◽

Manuel J. Fragoso-Vázquez ◽

Berenice P. Martel ◽

Alma Chávez-Blanco ◽

Alfonso Dueñas-González ◽

...

Keyword(s):

Valproic Acid ◽

Cell Lines ◽

Water Solubility ◽

Md Simulations ◽

Pamam Dendrimer ◽

Pamam Dendrimers ◽

Force Microscopy ◽

Micromolar Concentration ◽

Atomic Force

Background: Our research group has developed some Valproic Acid (VPA) derivatives employed as anti-proliferative compounds targeting the HDAC8 enzyme. However, some of these compounds are poorly soluble in water. Objective: Employed the four generations of Polyamidoamine (G4 PAMAM) dendrimers as drug carriers of these compounds to increase their water solubility for further in vitro evaluation. Methods: VPA derivatives were subjected to Docking and Molecular Dynamics (MD) simulations to evaluate their affinity on G4 PAMAM. Then, HPLC-UV/VIS, 1H NMR, MALDI-TOF and atomic force microscopy were employed to establish the formation of the drug-G4 PAMAM complexes. Results: The docking results showed that the amide groups of VPA derivatives make polar interactions with G4 PAMAM, whereas MD simulations corroborated the stability of the complexes. HPLC UV/VIS experiments showed an increase in the drug water solubility which was found to be directly proportional to the amount of G4 PAMAM. 1H NMR showed a disappearance of the proton amine group signals, correlating with docking results. MALDI-TOF and atomic force microscopy suggested the drug-G4 PAMAM dendrimer complexes formation. Discussion: In vitro studies showed that G4 PAMAM has toxicity in the micromolar concentration in MDAMB- 231, MCF7, and 3T3-L1 cell lines. VPA CF-G4 PAMAM dendrimer complex showed anti-proliferative properties in the micromolar concentration in MCF-7 and 3T3-L1, and in the milimolar concentration in MDAMB- 231, whereas VPA MF-G4 PAMAM dendrimer complex didn’t show effects on the three cell lines employed. Conclusion: These results demonstrate that G4 PAMAM dendrimers are capableof transporting poorly watersoluble aryl-VPA derivate compounds to increase its cytotoxic activity against neoplastic cell lines.

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Development and Optimization of Sustained Release Moxifloxacin Hydrochloride Loaded Nanoemulsion for Ophthalmic Drug Delivery: A 32 Factorial Design Approach

Micro and Nanosystems ◽

10.2174/1876402912999200826111031 ◽

2020 ◽

Vol 12 ◽

Author(s):

Sagar R. Pardeshi ◽

Harshal A. Mistari ◽

Rakhi S. Jain ◽

Pankaj R. Pardeshi ◽

Rahul L. Rajput ◽

...

Keyword(s):

Drug Release ◽

Sustained Release ◽

Factorial Design ◽

Water Solubility ◽

Tween 80 ◽

Drug Release Profile ◽

Sustained Drug Release ◽

Bacterial Conjunctivitis ◽

Promising Alternative

Background: Moxifloxacin is a BCS class I drug used in the treatment of bacterial conjunctivitis and keratitis. Despite its high water solubility, it possesses limited bioavailability due to anatomical and physiological constraints associated with the eyes which required multiple administrations to achieve a therapeutic effect. Objective: In order to prolong drug release and to improve antibacterial efficacy for the treatment of bacterial keratitis and conjunctivitis, moxifloxacin loaded nanoemulsion was developed. Methods: The concentration of oil (oleic acid), surfactant (tween 80), and cosurfactant (propylene glycol) were optimized by employing a 3-level 2-factorial design of experiment for the development of nanoemulsion. The developed nanoemulsion was characterized by particle size distribution, viscosity, refractive index, pH, drug content and release, transmission electron microscopy (TEM), and antibacterial study. The compatibility of the drug with the excipients was accessed by Fourier transform infrared spectroscopy (FTIR). Result: The average globule size was found to be 198.20 nm. The TEM study reveals the globules were nearly spherical and are well distributed. In vitro drug release profile for nanoemulsion shown sustained drug release (60.12% at the end of 6 h) compared to drug solution, where complete drug released within 2 h. The antibacterial effectiveness of the drug-loaded nanoemulsion was improved against S. aureus compared with the marketed formulation. Conclusion: The formulated sustained release nanoemulsion could be a promising alternative to eye drop with improved patient compliance by minimizing dosing frequency with improved antibacterial activity.

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Immuno-compatibility of desaminotyrosine and desaminotyrosyl tyrosine functionalized star-shaped oligo(ethylene glycol)s with different molecular weights

MRS Proceedings ◽

10.1557/opl.2015.327 ◽

2015 ◽

Vol 1718 ◽

pp. 97-102 ◽

Cited By ~ 1

Author(s):

Toralf Roch ◽

Konstanze K. Julich-Gruner ◽

Axel T. Neffe ◽

Nan Ma ◽

Andreas Lendlein

Keyword(s):

Aqueous Solution ◽

Ethylene Glycol ◽

Average Molecular Weight ◽

Molecular Weights ◽

Immunological Effects ◽

Microbial Products ◽

Low Levels ◽

Chain Lengths ◽

Immunological Evaluation

ABSTRACTPolymer-based therapeutic strategies require biomaterials with properties and functions tailored to the demands of specific applications leading to an increasing number of newly designed polymers. For the evaluation of those new materials, comprehensive biocompatibility studies including cyto-, tissue-, and immunocompatibility are essential. Recently, it could be demonstrated that star-shaped amino oligo(ethylene glycol)s (sOEG) with a number average molecular weight of 5 kDa and functionalized with the phenol-derived moieties desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) behave in aqueous solution like surfactants without inducing a substantial cytotoxicity, which may qualify them as solubilizer for hydrophobic drugs in aqueous solution. However, for biomedical applications the polymer solutions need to be free of immunogenic contaminations, which could result from inadequate laboratory environment or contaminated starting material. Furthermore, the materials should not induce uncontrolled or undesired immunological effects arising from material intrinsic properties. Therefore, a comprehensive immunological evaluation as perquisite for application of each biomaterial batch is required. This study investigated the immunological properties of sOEG-DAT(T) solutions, which were prepared using sOEG with number average molecular weights of 5 kDa, 10 kDa, and 20 kDa allowing analyzing the influence of the sOEG chain lengths on innate immune mechanisms. A macrophage-based assay was used to first demonstrate that all DAT(T)-sOEG solutions are free of endotoxins and other microbial contaminations such as fungal products. In the next step, the capacity of the different DAT(T)-functionalized sOEG solutions to induce cytokine secretion and generation of reactive oxygen species (ROS) was investigated using whole human blood. It was observed that low levels of the pro-inflammatory cytokines interleukin(IL)-1β and IL-6 were detected for all sOEG solutions but only when used at concentrations above 250 µg·mL-1. Furthermore, only the 20 kDa sOEG-DAT induced low amounts of ROS-producing monocytes. Conclusively, the data indicate that the materials were not contaminated with microbial products and do not induce substantial immunological adverse effectsin vitro,which is a prerequisite for future biological applications.

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The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

Cancers ◽

10.3390/cancers13040855 ◽

2021 ◽

Vol 13 (4) ◽

pp. 855

Author(s):

Paola Serrano Martinez ◽

Lorena Giuranno ◽

Marc Vooijs ◽

Robert P. Coppes

Keyword(s):

Signaling Pathways ◽

Progenitor Cells ◽

Tissue Regeneration ◽

Normal Tissue ◽

Cellular Response ◽

Adult Tissue ◽

Tissue Specific ◽

Radiation Induced

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

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Nanoformulation and Evaluation of Oral Berberine-Loaded Liposomes

Molecules ◽

10.3390/molecules26092591 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2591

Author(s):

Thuan Thi Duong ◽

Antti Isomäki ◽

Urve Paaver ◽

Ivo Laidmäe ◽

Arvo Tõnisoo ◽

...

Keyword(s):

Thin Film ◽

Drug Release ◽

Size Distribution ◽

Water Soluble ◽

Release Behavior ◽

Uniform Size ◽

Ethanol Injection ◽

Drug Release Behavior ◽

Poorly Water Soluble

Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.

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Optimization of the preparation process of mung bean puffed infant rice cereal and evaluation of the structure and digestion characteristics of starch

International Journal of Food Engineering ◽

10.1515/ijfe-2020-0025 ◽

2020 ◽

Vol 16 (8) ◽

Author(s):

Jiabao Cao ◽

Baoxin Lu ◽

Dongjie Zhang ◽

Longkui Cao ◽

Xia Wang ◽

...

Keyword(s):

Mung Bean ◽

Water Solubility ◽

Raw Materials ◽

Xrd Analysis ◽

Particle Structure ◽

Screw Speed ◽

Nutrient Analysis ◽

Shaped Particle ◽

Feed Moisture

AbstractThe present study was carried out to produce a high quality puffed infant rice cereal from rice and mung bean through extrusion technology. Experiments were designed using 3 independent variables (i. e. 14–18% feed moisture, 400–550 r/min screw speed and 125–175 °C barrel temperature) and 3 response variables (i. e. bulk density, water solubility index and degree of gelatinisation) at five different levels of central composite rotatable design (CCRD). The results of optimization demonstrated that 14% feed moisture, 400 r/min screw speed and 175 °C barrel temperature could generate rice-mungbean extrudates with desirable functional properties. The selected extrudate samples were further examined using scanning electron microscope (SEM), rapid viscosity analyzer (RVA), Fourier transform infrared spectrometer (FTIR), X-ray diffraction (XRD) analysis, in vitro digestibility and fundamental nutrient analysis. Notably, the initial oval-shaped particle structure of starch in the raw materials disappeared, the surface debris and roughness increased, and the density decreased. The time required for the gelatinization of puffed infant rice cereal was the shortest, which was in agreement with the positioning of ready-to-eat weaning food for infants. Moreover, the puffed infant rice cereal displayed higher peak viscosity and breakdown value, smaller retrogradation value and greater top taste value compared to the commercial infant rice cereal. Besides maintaining the initial characteristic peak of starch, the puffed infant rice cereal demonstrated characteristic absorption peaks of COO- in the vicinity of 1546 cm−1 and 1437 cm−1, indicating the formation of carboxylate during extrusion. In addition, the puffed infant rice cereal exhibited firm diffraction peaks at the diffraction angles of 7.4°, 12.5° and 20.5°, indicating that a certain amount of starch changed from type A to type V. Furthermore, the digestive rate of puffed infant rice cereal was higher than that of commercial infant cereal (90.21 versus 86.96%, respectively; p < 0.05). Altogether, our findings reveal that the developed puffed infant rice cereal meets the standards set by the Codex Alimentarius Commission (CAC; 74-1981).

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