Moussab/ORKG-training-evaluation-set huggingface dataset:
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: Radiotherapy
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 — keywords: Resveratrol
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 — Uses drug: Resveratrol
Research field: Medicinal Chemistry and Pharmaceutics
Title: Glycosylated Sertraline-Loaded Liposomes for Brain Targeting: QbD Study of Formulation Variabilities and Brain Transport
Abstract: Effectiveness of CNS-acting drugs depends on the localization, targeting, and capacity to be transported through the blood–brain barrier (BBB) which can be achieved by designing brain-targeting delivery vectors. Hence, the objective of this study was to screen the formulation and process variables affecting the performance of sertraline (Ser-HCl)-loaded pegylated and glycosylated liposomes. The prepared vectors were characterized for Ser-HCl entrapment, size, surface charge, release behavior, and in vitro transport through the BBB. Furthermore, the compatibility among liposomal components was assessed using SEM, FTIR, and DSC analysis. Through a thorough screening study, enhancement of Ser-HCl entrapment, nanosized liposomes with low skewness, maximized stability, and controlled drug leakage were attained. The solid-state characterization revealed remarkable interaction between Ser-HCl and the charging agent to determine drug entrapment and leakage. Moreover, results of liposomal transport through mouse brain endothelialpolyoma cells demonstrated greater capacity of the proposed glycosylated liposomes to target the cerebellar due to its higher density of GLUT1 and higher glucose utilization. This transport capacity was confirmed by the inhibiting action of both cytochalasin B and phenobarbital. Using C6 glioma cells model, flow cytometry, time-lapse live cell imaging, and in vivo NIR fluorescence imaging demonstrated that optimized glycosylated liposomes can be transported through the BBB by classical endocytosis, as well as by specific transcytosis. In conclusion, the current study proposed a thorough screening of important formulation and process variabilities affecting brain-targeting liposomes for further scale-up processes.
Extracted statement — Uses drug: Sertraline
Research field: Medicinal Chemistry and Pharmaceutics
Title: Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles
Abstract: Abstract It is very challenging to treat brain cancer because of the blood–brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.
Extracted statement — Uses drug: siRNA
Research field: Medicinal Chemistry and Pharmaceutics
Title: The Influence of Drug Physical State on the Dissolution Enhancement of Solid Dispersions Prepared Via Hot-Melt Extrusion: A Case Study Using Olanzapine
Abstract: In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug–polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated fully amorphous dispersions with OLZ, whereas the formulations with PVPVA and SLP contained 14%–16% crystalline OLZ. Increasing the extrusion temperature to 180°C allowed the preparation of fully amorphous systems with PVPVA and SLP. Despite these differences, the dissolution rates of these preparations were comparable, with PVP showing a lower release rate despite being fully amorphous. These findings suggested that, at least in the particular case of OLZ, the absence of crystalline material may not be critical to the dissolution performance. We suggest alternative key factors determining dissolution, particularly the dissolution behavior of the polymers themselves.
Extracted statement — Carrier for hot melt extrusion: Soluplus®
Research field: Medicinal Chemistry and Pharmaceutics
Title: Solid-state characterization of Felodipine–Soluplus amorphous solid dispersions
Abstract: Abstract The aim of the current study is to develop amorphous solid dispersion (SD) via hot melt extrusion technology to improve the solubility of a water-insoluble compound, felodipine (FEL). The solubility was dramatically increased by preparation of amorphous SDs via hot-melt extrusion with an amphiphilic polymer, Soluplus® (SOL). FEL was found to be miscible with SOL by calculating the solubility parameters. The solubility of FEL within SOL was determined to be in the range of 6.2–9.9% (w/w). Various techniques were applied to characterize the solid-state properties of the amorphous SDs. These included Fourier Transform Infrared Spectrometry spectroscopy and Raman spectroscopy to detect the formation of hydrogen bonding between the drug and the polymer. Scanning electron microscopy was performed to study the morphology of the SDs. Among all the hot-melt extrudates, FEL was found to be molecularly dispersed within the polymer matrix for the extrudates containing 10% drug, while few small crystals were detected in the 30 and 50% extrudates. In conclusion, solubility of FEL was enhanced while a homogeneous SD was achieved for 10% drug loading.
Extracted statement — Carrier for hot melt extrusion: Soluplus®
Research field: Medicinal Chemistry and Pharmaceutics
Title: Development of In Vitro–In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls
Abstract: Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls.
Extracted statement — Uses drug: Suvorexant
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 — Uses drug: Tamoxifen
Research field: Medicinal Chemistry and Pharmaceutics
Title: Ferumoxytol for treatment of iron deficiency anemia in patients with chronic kidney disease
Abstract: Background: Iron deficiency anemia (IDA) is a common problem in patients with chronic kidney disease (CKD). Use of intravenous (i.v.) iron effectively treats the resultant anemia, but available iron products have side effects or dosing regimens that limit safety and convenience. Objective: Ferumoxytol (Feraheme™) is a new i.v. iron product recently approved for use in treatment of IDA in CKD patients. This article reviews the structure, pharmacokinetics, and clinical trial results on ferumoxytol. The author also offers his opinions on the role of this product in clinical practice. Methods: This review encompasses important information contained in clinical and preclinical studies of ferumoxytol and is supplemented with information from the US Food and Drug Administration. Results/conclusion: Ferumoxytol offers substantial safety and superior efficacy compared with oral iron therapy. As ferumoxytol can be administered as 510 mg in < 1 min, it is substantially more convenient than other iron products in nondialysis patients. Although further experience with this product is needed in patients at higher risk of drug reactions, ferumoxytol is likely to be highly useful in the hospital and outpatient settings for treatment of IDA.
Extracted statement — Field of application: Therapy
Research field: Medicinal Chemistry and Pharmaceutics
Title: In vivo biodistribution of venlafaxine-PLGA nanoparticles for brain delivery: plain vs. functionalized nanoparticles
Abstract: ABSTRACT Background: Actually, no drugs provide therapeutic benefit to approximately one-third of depressed patients. Depression is predicted to become the first global disease by 2030. So, new therapeutic interventions are imperative. Research design and methods: Venlafaxine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were surface functionalized with two ligands against transferrin receptor to enhance access to brain. An in vitro blood–brain barrier model using hCMEC/D3 cell line was developed to evaluate permeability. In vivo biodistribution studies were performed using C57/bl6 mice. Particles were administered intranasal and main organs were analyzed. Results: Particles were obtained as a lyophilized powder easily to re-suspend. Internalization and permeability studies showed the following cell association sequence: TfRp-NPs>Tf-NPs>plain NPs. Permeability studies also showed that encapsulated VLF was not affected by P-gP pump efflux increasing its concentration in the basolateral side after 24 h. In vivo studies showed that 25% of plain NPs reach the brain after 30 min of one intranasal administration while less than 5% of functionalized NPs get the target. Conclusions: Plain NPs showed the highest ability to reach the brain vs. functionalized NPs after 30 min by intranasal administration. We suggest plain NPs probably travel via direct nose-to-brian route whereas functionalized NPs reach the brain by receptor-mediated endocytosis.
Extracted statement — Uses drug: Venlafaxine
Research field: Medicinal Chemistry and Pharmaceutics
Title: Vincristine and temozolomide combined chemotherapy for the treatment of glioma: a comparison of solid lipid nanoparticles and nanostructured lipid carriers for dual drugs delivery
Abstract: Abstract Context: Glioma is a common malignant brain tumor originating in the central nervous system. Efficient delivery of therapeutic agents to the cells and tissues is a difficult challenge. Co-delivery of anticancer drugs into the cancer cells or tissues by multifunctional nanocarriers may provide a new paradigm in cancer treatment. Objective: In this study, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were constructed for co-delivery of vincristine (VCR) and temozolomide (TMZ) to develop the synergetic therapeutic action of the two drugs. The antitumor effects of these two systems were compared to provide a better choice for gliomatosis cerebri treatment. Methods: VCR- and TMZ-loaded SLNs (VT-SLNs) and NLCs (VT-NLCs) were formulated. Their particle size, zeta potential, drug encapsulation efficiency (EE) and drug loading capacity were evaluated. The single TMZ-loaded SLNs and NLCs were also prepared as contrast. Anti-tumor efficacies of the two kinds of carriers were evaluated on U87 malignant glioma cells and mice bearing malignant glioma model. Results: Significantly better glioma inhibition was observed on NLCs formulations than SLNs, and dual drugs displayed the highest antitumor efficacy in vivo and in vitro than all the other formulations used. Conclusion: VT-NLCs can deliver VCR and TMZ into U87MG cells more efficiently, and inhibition efficacy is higher than VT-SLNs. This dual drugs-loaded NLCs could be an outstanding drug delivery system to achieve excellent therapeutic efficiency for the treatment of malignant gliomatosis cerebri.
Extracted statement — Uses drug: Vincristine
Research field: Medicinal Chemistry and Pharmaceutics
Title: Inhaled Voriconazole for Prevention of Invasive Pulmonary Aspergillosis
Abstract: ABSTRACT Targeted airway delivery of antifungals as prophylaxis against invasive aspergillosis may lead to high lung drug concentrations while avoiding toxicities associated with systemically administered agents. We evaluated the effectiveness of aerosolizing the intravenous formulation of voriconazole as prophylaxis against invasive pulmonary aspergillosis caused by Aspergillus fumigatus in an established murine model. Inhaled voriconazole significantly improved survival and limited the extent of invasive disease, as assessed by histopathology, compared to control and amphotericin B treatments.
Extracted statement — Uses drug: Voriconazole
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 — Composition: Water