Moussab/ORKG-training-evaluation-set huggingface dataset:
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: Paclitaxel
Research field: Medicinal Chemistry and Pharmaceutics
Title: Functionalization of Silver Nanoparticles Loaded with Paclitaxel-induced A549 Cells Apoptosis Through ROS-Mediated Signaling Pathways
Abstract: Background: Paclitaxel (PTX) is one of the most important and effective anticancer drugs for the treatment of human cancer. However, its low solubility and severe adverse effects limited clinical use. To overcome this limitation, nanotechnology has been used to overcome tumors due to its excellent antimicrobial activity. Objective: This study was to demonstrate the anticancer properties of functionalization silver nanoparticles loaded with paclitaxel (Ag@PTX) induced A549 cells apoptosis through ROS-mediated signaling pathways. Methods: The Ag@PTX nanoparticles were charged with a zeta potential of about -17 mv and characterized around 2 nm with a narrow size distribution. Results: Ag@PTX significantly decreased the viability of A549 cells and possessed selectivity between cancer and normal cells. Ag@PTX induced A549 cells apoptosis was confirmed by nuclear condensation, DNA fragmentation, and activation of caspase-3. Furthermore, Ag@PTX enhanced the anti-cancer activity of A549 cells through ROS-mediated p53 and AKT signalling pathways. Finally, in a xenograft nude mice model, Ag@PTX suppressed the growth of tumors. Conclusion: Our findings suggest that Ag@PTX may be a candidate as a chemopreventive agent and could be a highly efficient way to achieve anticancer synergism for human cancers.
Extracted statement — keywords: Paclitaxel
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 — Uses drug: Paclitaxel
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 — Uses drug: Paclitaxel
Research field: Medicinal Chemistry and Pharmaceutics
Title: Formulation, optimization, hemocompatibility and pharmacokinetic evaluation of PLGA nanoparticles containing paclitaxel
Abstract: Abstract Objective: Paclitaxel (PTX)-loaded polymer (Poly(lactic-co-glycolic acid), PLGA)-based nanoformulation was developed with the objective of formulating cremophor EL-free nanoformulation intended for intravenous use. Significance: The polymeric PTX nanoparticles free from the cremophor EL will help in eliminating the shortcomings of the existing delivery system as cremophor EL causes serious allergic reactions to the subjects after intravenous use. Methods and results: Paclitaxel-loaded nanoparticles were formulated by nanoprecipitation method. The diminutive nanoparticles (143.2 nm) with uniform size throughout (polydispersity index, 0.115) and high entrapment efficiency (95.34%) were obtained by employing the Box–Behnken design for the optimization of the formulation with the aid of desirability approach-based numerical optimization technique. Optimized levels for each factor viz. polymer concentration (X1), amount of organic solvent (X2), and surfactant concentration (X3) were 0.23%, 5 ml %, and 1.13%, respectively. The results of the hemocompatibility studies confirmed the safety of PLGA-based nanoparticles for intravenous administration. Pharmacokinetic evaluations confirmed the longer retention of PTX in systemic circulation. Conclusion: In a nutshell, the developed polymeric nanoparticle formulation of PTX precludes the inadequacy of existing PTX formulation and can be considered as superior alternative carrier system of the same.
Extracted statement — Uses drug: Paclitaxel
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 — Uses drug: Paclitaxel
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 — Uses drug: Paclitaxel
Research field: Medicinal Chemistry and Pharmaceutics
Title: Targeted Delivery of Insoluble Cargo (Paclitaxel) by PEGylated Chitosan Nanoparticles Grafted with Arg-Gly-Asp (RGD)
Abstract: Poor delivery of insoluble anticancer drugs has so far precluded their clinical application. In this study, we developed a tumor-targeting delivery system for insoluble drug (paclitaxel, PTX) by PEGylated O-carboxymethyl-chitosan (CMC) nanoparticles grafted with cyclic Arg-Gly-Asp (RGD) peptide. To improve the loading efficiency (LE), we combined O/W/O double emulsion method with temperature-programmed solidification technique and controlled PTX within the matrix network as in situ nanocrystallite form. Furthermore, these CMC nanoparticles were PEGylated, which could reduce recognition by the reticuloendothelial system (RES) and prolong the circulation time in blood. In addition, further graft of cyclic RGD peptide at the terminal of PEG chain endowed these nanoparticles with higher affinity to in vitro Lewis lung carcinoma (LLC) cells and in vivo tumor tissue. These outstanding properties enabled as-designed nanodevice to exhibit a greater tumor growth inhibition effect and much lower side effects over the commercial formulation Taxol.
Extracted statement — Uses drug: Paclitaxel
Research field: Medicinal Chemistry and Pharmaceutics
Title: Targeted Paclitaxel by Conjugation to Iron Oxide and Gold Nanoparticles
Abstract: The Fe(3)O(4) nanoparticles, tailored with maleimidyl 3-succinimidopropionate ligands, were conjugated with paclitaxel molecules that were attached with a poly(ethylene glycol) (PEG) spacer through a phosphodiester moiety at the (C-2')-OH position. The average number of paclitaxel molecules/nanoparticles was determined as 83. These nanoparticles liberated paclitaxel molecules upon exposure to phosphodiesterase.
Extracted statement — Uses drug: Paclitaxel
Research field: Medicinal Chemistry and Pharmaceutics
Title: Functionalization of Silver Nanoparticles Loaded with Paclitaxel-induced A549 Cells Apoptosis Through ROS-Mediated Signaling Pathways
Abstract: Background: Paclitaxel (PTX) is one of the most important and effective anticancer drugs for the treatment of human cancer. However, its low solubility and severe adverse effects limited clinical use. To overcome this limitation, nanotechnology has been used to overcome tumors due to its excellent antimicrobial activity. Objective: This study was to demonstrate the anticancer properties of functionalization silver nanoparticles loaded with paclitaxel (Ag@PTX) induced A549 cells apoptosis through ROS-mediated signaling pathways. Methods: The Ag@PTX nanoparticles were charged with a zeta potential of about -17 mv and characterized around 2 nm with a narrow size distribution. Results: Ag@PTX significantly decreased the viability of A549 cells and possessed selectivity between cancer and normal cells. Ag@PTX induced A549 cells apoptosis was confirmed by nuclear condensation, DNA fragmentation, and activation of caspase-3. Furthermore, Ag@PTX enhanced the anti-cancer activity of A549 cells through ROS-mediated p53 and AKT signalling pathways. Finally, in a xenograft nude mice model, Ag@PTX suppressed the growth of tumors. Conclusion: Our findings suggest that Ag@PTX may be a candidate as a chemopreventive agent and could be a highly efficient way to achieve anticancer synergism for human cancers.
Extracted statement — Uses drug: Paclitaxel
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 — Uses drug: Paclitaxel
Research field: Medicinal Chemistry and Pharmaceutics
Title: Hybrid Nanocrystals: Achieving Concurrent Therapeutic and Bioimaging Functionalities toward Solid Tumors
Abstract: Bioimaging and therapeutic agents accumulated in ectopic tumors following intravenous administration of hybrid nanocrystals to tumor-bearing mice. Solid, nanosized paclitaxel crystals physically incorporated fluorescent molecules throughout the crystal lattice and retained fluorescent properties in the solid state. Hybrid nanocrystals were significantly localized in solid tumors and remained in the tumor for several days. An anticancer effect is expected of these hybrid nanocrystals.
Extracted statement — Uses drug: Paclitaxel
Research field: Medicinal Chemistry and Pharmaceutics
Title: Influence of Hydroxypropyl β-Cyclodextrin on the Corneal Permeation of Pilocarpine
Abstract: Abstract The influence of hydroxypropyl β-cyclodextrin (HPβCD) on the corneal permeation of pilocarpine nitrate was investigated by an in vitro permeability study using isolated rabbit cornea. Pupillary-response pattern to pilocarpine nitrate with and without HPβCD was examined in rabbit eye. Corneal permeation of pilocarpine nitrate was found to be four times higher after adding HPβCD into the formulation. The reduction of pupil diameter (miosis) by pilocarpine nitrate was significantly increased as a result of HPβCD addition into the simple aqueous solution of the active substance. The highest miotic response was obtained with the formulation prepared in a vehicle of Carbopol® 940. It is suggested that ocular bioavailability of pilocarpine nitrate could be improved by the addition of HPβCD.
Extracted statement — Uses drug: Pilocarpine
Research field: Medicinal Chemistry and Pharmaceutics
Title: Low active loading of cargo into engineered extracellular vesicles results in inefficient miRNA mimic delivery
Abstract: ABSTRACT Extracellular vesicles (EVs) hold great potential as novel systems for nucleic acid delivery due to their natural composition. Our goal was to load EVs with microRNA that are synthesized by the cells that produce the EVs. HEK293T cells were engineered to produce EVs expressing a lysosomal associated membrane, Lamp2a fusion protein. The gene encoding pre-miR-199a was inserted into an artificial intron of the Lamp2a fusion protein. The TAT peptide/HIV-1 transactivation response (TAR) RNA interacting peptide was exploited to enhance the EV loading of the pre-miR-199a containing a modified TAR RNA loop. Computational modeling demonstrated a stable interaction between the modified pre-miR-199a loop and TAT peptide. EMSA gel shift, recombinant Dicer processing and luciferase binding assays confirmed the binding, processing and functionality of the modified pre-miR-199a. The TAT-TAR interaction enhanced the loading of the miR-199a into EVs by 65-fold. Endogenously loaded EVs were ineffective at delivering active miR-199a-3p therapeutic to recipient SK-Hep1 cells. While the low degree of miRNA loading into EVs through this approach resulted in inefficient distribution of RNA cargo into recipient cells, the TAT TAR strategy to load miRNA into EVs may be valuable in other drug delivery approaches involving miRNA mimics or other hairpin containing RNAs.
Extracted statement — Cargo: Pre-miR-199a
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 — Cargo: Protein
Research field: Medicinal Chemistry and Pharmaceutics
Title: Evaluation of psoralen ethosomes for topical delivery in rats by using in vivo microdialysis
Abstract: This study aimed to improve skin permeation and deposition of psoralen by using ethosomes and to investigate real-time drug release in the deep skin in rats. We used a uniform design method to evaluate the effects of different ethosome formulations on entrapment efficiency and drug skin deposition. Using in vitro and in vivo methods, we investigated skin penetration and release from psoralen-loaded ethosomes in comparison with an ethanol tincture. In in vitro studies, the use of ethosomes was associated with a 6.56-fold greater skin deposition of psoralen than that achieved with the use of the tincture. In vivo skin microdialysis showed that the peak concentration and area under the curve of psoralen from ethosomes were approximately 3.37 and 2.34 times higher, respectively, than those of psoralen from the tincture. Moreover, it revealed that the percutaneous permeability of ethosomes was greater when applied to the abdomen than when applied to the chest or scapulas. Enhanced permeation and skin deposition of psoralen delivered by ethosomes may help reduce toxicity and improve the efficacy of long-term psoralen treatment.
Extracted statement — Uses drug: Psoralen