Moussab/ORKG-training-evaluation-set huggingface dataset:
Research field: Medicinal Chemistry and Pharmaceutics
Title: Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles
Abstract: Worldwide outbreaks of infectious diseases necessitate the development of rapid and accurate diagnostic methods. Colorimetric assays are a representative tool to simply identify the target molecules in specimens through color changes of an indicator (e.g., nanosized metallic particle, and dye molecules). The detection method is used to confirm the presence of biomarkers visually and measure absorbance of the colored compounds at a specific wavelength. In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under positive electrolyte (e.g., 0.1 M MgCl2) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This platform is able to verify the existence of viral molecules through a localized surface plasmon resonance (LSPR) shift and color changes of AuNPs in the UV–vis wavelength range. We designed a pair of thiol-modified probes at either the 5′ end or 3′ end to organize complementary base pairs with upstream of the E protein gene (upE) and open reading frames (ORF) 1a on MERS-CoV. The dsDNA of the target and probes forms a disulfide-induced long self-assembled complex, which protects AuNPs from salt-induced aggregation and transition of optical properties. This colorimetric assay could discriminate down to 1 pmol/μL of 30 bp MERS-CoV and further be adapted for convenient on-site detection of other infectious diseases, especially in resource-limited settings.
Extracted statement — Mechanism of Antiviral Action: Color changes of AuNPs
Research field: Medicinal Chemistry and Pharmaceutics
Title: Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro
Abstract: Radioresistant hypoxic cells may contribute to the failure of radiation therapy in controlling certain tumors. Some studies have suggested the radiosensitizing effect of paclitaxel. The poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The morphology of the two human tumor cell lines: a carcinoma cervicis (HeLa) and a hepatoma (HepG2), treated with paclitaxel-loaded nanoparticles was photomicrographed. Flow cytometry was used to quantify the number of the tumor cells held in the G2/M phase of the cell cycle. The cellular uptake of nanoparticles was evaluated by transmission electronic microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 200nm and 800nm. The encapsulation efficiency was 85.5％. The release behaviour of paclitaxel from the nanoparticles exhibited a biphasic pattern characterised by a fast initial release during the first 24 h, followed by a slower and continuous release. Co-culture of the two tumor cell lines with paclitaxel-loaded nanoparticles demonstrated that the cell morphology was changed and the released paclitaxel retained its bioactivity to block cells in the G2/M phase. The cellular uptake of nanoparticles was observed. The free paclitaxel and paclitaxel-loaded nanoparticles effectively sensitized hypoxic HeLa and HepG2 cells to radiation. Under this experimental condition, the radiosensitization of paclitaxel-loaded nanoparticles was more significant than that of free paclitaxel.Keywords: Paclitaxel；Drug delivery；Nanoparticle；Radiotherapy；Hypoxia；Human tumor cells；cellular uptake
Extracted statement — keywords: Drug delivery
Research field: Medicinal Chemistry and Pharmaceutics
Title: Oral delivery of anti-TNF antibody shielded by natural polyphenol-mediated supramolecular assembly for inflammatory bowel disease therapy
Abstract: Rationale: Anti-tumor necrosis factor (TNF) therapy is a very effective way to treat inflammatory bowel disease. However, systemic exposure to anti-TNF-α antibodies through current clinical systemic administration can cause serious adverse effects in many patients. Here, we report a facile prepared self-assembled supramolecular nanoparticle based on natural polyphenol tannic acid and poly(ethylene glycol) containing polymer for oral antibody delivery. Method: This supramolecular nanoparticle was fabricated within minutes in aqueous solution and easily scaled up to gram level due to their pH-dependent reversible assembly. DSS-induced colitis model was prepared to evaluate the ability of inflammatory colon targeting ability and therapeutic efficacy of this antibody-loaded nanoparticles. Results: This polyphenol-based nanoparticle can be aqueous assembly without organic solvent and thus scaled up easily. The oral administration of antibody loaded nanoparticle achieved high accumulation in the inflamed colon and low systemic exposure. The novel formulation of anti-TNF-α antibodies administrated orally achieved high efficacy in the treatment of colitis mice compared with free antibodies administered orally. The average weight, colon length, and inflammatory factors in colon and serum of colitis mice after the treatment of novel formulation of anti-TNF-α antibodies even reached the similar level to healthy controls. Conclusion: This polyphenol-based supramolecular nanoparticle is a promising platform for oral delivery of antibodies for the treatment of inflammatory bowel diseases, which may have promising clinical translation prospects.
Extracted statement — Colitis model: DSS-induced colitis
Research field: Medicinal Chemistry and Pharmaceutics
Title: Exosome-based nanocarriers as bio-inspired and versatile vehicles for drug delivery: recent advances and challenges
Abstract: Recent decades have witnessed the fast and impressive development of nanocarriers as a drug delivery system. Considering the safety, delivery efficiency and stability of nanocarriers, there are many obstacles in accomplishing successful clinical translation of these nanocarrier-based drug delivery systems. The gap has urged drug delivery scientists to develop innovative nanocarriers with high compatibility, stability and longer circulation time. Exosomes are nanometer-sized, lipid-bilayer-enclosed extracellular vesicles secreted by many types of cells. Exosomes serving as versatile drug vehicles have attracted increasing attention due to their inherent ability of shuttling proteins, lipids and genes among cells and their natural affinity to target cells. Attractive features of exosomes, such as nanoscopic size, low immunogenicity, high biocompatibility, encapsulation of various cargoes and the ability to overcome biological barriers, distinguish them from other nanocarriers. To date, exosome-based nanocarriers delivering small molecule drugs as well as bioactive macromolecules have been developed for the treatment of many prevalent and obstinate diseases including cancer, CNS disorders and some other degenerative diseases. Exosome-based nanocarriers have a huge prospect in overcoming many hindrances encountered in drug and gene delivery. This review highlights the advances as well as challenges of exosome-based nanocarriers as drug vehicles. Special focus has been placed on the advantages of exosomes in delivering various cargoes and in treating obstinate diseases, aiming to offer new insights for exploring exosomes in the field of drug delivery.
Extracted statement — Type of nanocarrier: Extracellular vesicles
Research field: Medicinal Chemistry and Pharmaceutics
Title: A Novel Nanoparticle Formulation for Sustained Paclitaxel Delivery
Abstract: PurposeTo develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel.MethodsChitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231).ResultsThese studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC50 of PTX.ConclusionThese advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.
Extracted statement — Polymer: Glyceryl monooleate (GMO)
Research field: Medicinal Chemistry and Pharmaceutics
Title: Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro
Abstract: Radioresistant hypoxic cells may contribute to the failure of radiation therapy in controlling certain tumors. Some studies have suggested the radiosensitizing effect of paclitaxel. The poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e. encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The morphology of the two human tumor cell lines: a carcinoma cervicis (HeLa) and a hepatoma (HepG2), treated with paclitaxel-loaded nanoparticles was photomicrographed. Flow cytometry was used to quantify the number of the tumor cells held in the G2/M phase of the cell cycle. The cellular uptake of nanoparticles was evaluated by transmission electronic microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 200nm and 800nm. The encapsulation efficiency was 85.5％. The release behaviour of paclitaxel from the nanoparticles exhibited a biphasic pattern characterised by a fast initial release during the first 24 h, followed by a slower and continuous release. Co-culture of the two tumor cell lines with paclitaxel-loaded nanoparticles demonstrated that the cell morphology was changed and the released paclitaxel retained its bioactivity to block cells in the G2/M phase. The cellular uptake of nanoparticles was observed. The free paclitaxel and paclitaxel-loaded nanoparticles effectively sensitized hypoxic HeLa and HepG2 cells to radiation. Under this experimental condition, the radiosensitization of paclitaxel-loaded nanoparticles was more significant than that of free paclitaxel.Keywords: Paclitaxel；Drug delivery；Nanoparticle；Radiotherapy；Hypoxia；Human tumor cells；cellular uptake
Extracted statement — keywords: Human tumor cells
Research field: Medicinal Chemistry and Pharmaceutics
Title: Paclitaxel/Chitosan Nanosupensions Provide Enhanced Intravesical Bladder Cancer Therapy with Sustained and Prolonged Delivery of Paclitaxel
Abstract: Bladder cancer (BC) is a very common cancer. Nonmuscle-invasive bladder cancer (NMIBC) is the most common type of bladder cancer. After postoperative tumor resection, chemotherapy intravesical instillation is recommended as a standard treatment to significantly reduce recurrences. Nanomedicine-mediated delivery of a chemotherapeutic agent targeting cancer could provide a solution to obtain longer residence time and high bioavailability of an anticancer drug. The approach described here provides a nanomedicine with sustained and prolonged delivery of paclitaxel and enhanced therapy of intravesical bladder cancer, which is paclitaxel/chitosan (PTX/CS) nanosupensions (NSs). The positively charged PTX/CS NSs exhibited a rod-shaped morphology with a mean diameter about 200 nm. They have good dispersivity in water without any protective agents, and the positively charged properties make them easy to be adsorbed on the inner mucosa of the bladder through electrostatic adsorption. PTX/CS NSs also had a high drug loading capacity and can maintain sustained release of paclitaxel which could be prolonged over 10 days. Cell experiments in vitro demonstrated that PTX/CS NSs had good biocompatibility and effective bladder cancer cell proliferation inhibition. The significant anticancer efficacy against intravesical bladder cancer was verified by an in situ bladder cancer model. The paclitaxel/chitosan nanosupensions could provide sustained delivery of chemotherapeutic agents with significant anticancer efficacy against intravesical bladder cancer.
Extracted statement — keywords: intravesical instillation
Research field: Medicinal Chemistry and Pharmaceutics
Title: Cellular Uptake Mechanism of Paclitaxel Nanocrystals Determined by Confocal Imaging and Kinetic Measurement
Abstract: Nanocrystal formulation has become a viable solution for delivering poorly soluble drugs including chemotherapeutic agents. The purpose of this study was to examine cellular uptake of paclitaxel nanocrystals by confocal imaging and concentration measurement. It was found that drug nanocrystals could be internalized by KB cells at much higher concentrations than a conventional, solubilized formulation. The imaging and quantitative results suggest that nanocrystals could be directly taken up by cells as solid particles, likely via endocytosis. Moreover, it was found that polymer treatment to drug nanocrystals, such as surface coating and lattice entrapment, significantly influenced the cellular uptake. While drug molecules are in the most stable physical state, nanocrystals of a poorly soluble drug are capable of achieving concentrated intracellular presence enabling needed therapeutic effects.
Extracted statement — has cell line: KB cells
Research field: Medicinal Chemistry and Pharmaceutics
Title: PEG–lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication
Abstract: Abstract PEG–lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG–DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG–DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG–lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG–lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG–lipid micelles and their relevance to the inherent advantages and applications of PEG–lipid micelles for drug delivery.
Extracted statement — Type of nanocarrier: Lipid micelles
Research field: Medicinal Chemistry and Pharmaceutics
Title: Exosome-based nanocarriers as bio-inspired and versatile vehicles for drug delivery: recent advances and challenges
Abstract: Recent decades have witnessed the fast and impressive development of nanocarriers as a drug delivery system. Considering the safety, delivery efficiency and stability of nanocarriers, there are many obstacles in accomplishing successful clinical translation of these nanocarrier-based drug delivery systems. The gap has urged drug delivery scientists to develop innovative nanocarriers with high compatibility, stability and longer circulation time. Exosomes are nanometer-sized, lipid-bilayer-enclosed extracellular vesicles secreted by many types of cells. Exosomes serving as versatile drug vehicles have attracted increasing attention due to their inherent ability of shuttling proteins, lipids and genes among cells and their natural affinity to target cells. Attractive features of exosomes, such as nanoscopic size, low immunogenicity, high biocompatibility, encapsulation of various cargoes and the ability to overcome biological barriers, distinguish them from other nanocarriers. To date, exosome-based nanocarriers delivering small molecule drugs as well as bioactive macromolecules have been developed for the treatment of many prevalent and obstinate diseases including cancer, CNS disorders and some other degenerative diseases. Exosome-based nanocarriers have a huge prospect in overcoming many hindrances encountered in drug and gene delivery. This review highlights the advances as well as challenges of exosome-based nanocarriers as drug vehicles. Special focus has been placed on the advantages of exosomes in delivering various cargoes and in treating obstinate diseases, aiming to offer new insights for exploring exosomes in the field of drug delivery.
Extracted statement — Advantages: Low immunogenicity
Research field: Medicinal Chemistry and Pharmaceutics
Title: Enhanced delivery of etoposide across the blood–brain barrier to restrain brain tumor growth using melanotransferrin antibody- and tamoxifen-conjugated solid lipid nanoparticles
Abstract: Abstract Melanotransferrin antibody (MA) and tamoxifen (TX) were conjugated on etoposide (ETP)-entrapped solid lipid nanoparticles (ETP-SLNs) to target the blood–brain barrier (BBB) and glioblastom multiforme (GBM). MA- and TX-conjugated ETP-SLNs (MA–TX–ETP–SLNs) were used to infiltrate the BBB comprising a monolayer of human astrocyte-regulated human brain-microvascular endothelial cells (HBMECs) and to restrain the proliferation of malignant U87MG cells. TX-grafted ETP-SLNs (TX–ETP–SLNs) significantly enhanced the BBB permeability coefficient for ETP and raised the fluorescent intensity of calcein-AM when compared with ETP-SLNs. In addition, surface MA could increase the BBB permeability coefficient for ETP about twofold. The viability of HBMECs was higher than 86%, suggesting a high biocompatibility of MA–TX–ETP-SLNs. Moreover, the efficiency in antiproliferation against U87MG cells was in the order of MA–TX–ETP-SLNs > TX–ETP-SLNs > ETP-SLNs > SLNs. The capability of MA–TX–ETP-SLNs to target HBMECs and U87MG cells during internalization was verified by immunochemical staining of expressed melanotransferrin. MA–TX–ETP-SLNs can be a potent pharmacotherapy to deliver ETP across the BBB to GBM.
Extracted statement — Surface functionalized with: Melanotransferrin antibody (MA)
Research field: Medicinal Chemistry and Pharmaceutics
Title: Resveratrol loaded polymeric micelles for theranostic targeting of breast cancer cells
Abstract: Treatment of breast cancer underwent extensive progress in recent years with molecularly targeted therapies. However, non-specific pharmaceutical approaches (chemotherapy) persist, inducing severe side-effects. Phytochemicals provide a promising alternative for breast cancer prevention and treatment. Specifically, resveratrol (res) is a plant-derived polyphenolic phytoalexin with potent biological activity but displays poor water solubility, limiting its clinical use. Here we have developed a strategy for delivering res using a newly synthesized nano-carrier with the potential for both diagnosis and treatment. Methods: Res-loaded nanoparticles were synthesized by the emulsion method using Pluronic F127 block copolymer and Vitamin E-TPGS. Nanoparticle characterization was performed by SEM and tunable resistive pulse sensing. Encapsulation Efficiency (EE%) and Drug Loading (DL%) content were determined by analysis of the supernatant during synthesis. Nanoparticle uptake kinetics in breast cancer cell lines MCF-7 and MDA-MB-231 as well as in MCF-10A breast epithelial cells were evaluated by flow cytometry and the effects of res on cell viability via MTT assay. Results: Res-loaded nanoparticles with spherical shape and a dominant size of 179±22 nm were produced. Res was loaded with high EE of 73±0.9% and DL content of 6.2±0.1%. Flow cytometry revealed higher uptake efficiency in breast cancer cells compared to the control. An MTT assay showed that res-loaded nanoparticles reduced the viability of breast cancer cells with no effect on the control cells. Conclusions: These results demonstrate that the newly synthesized nanoparticle is a good model for the encapsulation of hydrophobic drugs. Additionally, the nanoparticle delivers a natural compound and is highly effective and selective against breast cancer cells rendering this type of nanoparticle an excellent candidate for diagnosis and therapy of difficult to treat mammary malignancies.
Extracted statement — Cytotoxicity assay: MTT assay
Research field: Medicinal Chemistry and Pharmaceutics
Title: Paclitaxel-loaded PLGA nanoparticles surface modified with transferrin and Pluronic®P85, anin vitrocell line andin vivobiodistribution studies on rat model
Abstract: The development of multidrug resistance (due to drug efflux by P-glycoproteins) is a major drawback with the use of paclitaxel (PTX) in the treatment of cancer. The rationale behind this study is to prepare PTX nanoparticles (NPs) for the reversal of multidrug resistance based on the fact that PTX loaded into NPs is not recognized by P-glycoproteins and hence is not effluxed out of the cell. Also, the intracellular penetration of the NPs could be enhanced by anchoring transferrin (Tf) on the PTX-PLGA-NPs. PTX-loaded PLGA NPs (PTX-PLGA-NPs), Pluronic®P85-coated PLGA NPs (P85-PTX-PLGA-NPs), and Tf-anchored PLGA NPs (Tf-PTX-PLGA-NPs) were prepared and evaluted for cytotoxicity and intracellular uptake using C6 rat glioma cell line. A significant increase in cytotoxicity was observed in the order of Tf-PTX-PLGA-NPs > P85-PTX-PLGA-NPs > PTX-PLGA-NPs in comparison to drug solution. In vivo biodistribution on male Sprague–Dawley rats bearing C6 glioma (subcutaneous) showed higher tumor PTX concentrations in animals administered with PTX-NPs compared to drug solution.
Extracted statement — keywords: multidrug resistance