Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of Crystallinity on the Properties of Polycaprolactone Nanoparticles Containing the Dual FLAP/mPEGS-1 Inhibitor BRP-187.

ABSTRACT: Seven polycaprolactones (PCL) with constant hydrophobicity but a varying degree of crystallinity prepared from the constitutional isomers ε-caprolactone (εCL) and δ-caprolactone (δCL) were utilized to formulate nanoparticles (NPs). The aim was to investigate the effect of the crystallinity of the bulk polymers on the enzymatic degradation of the particles. Furthermore, their efficiency to encapsulate the hydrophobic anti-inflammatory drug BRP-187 and the final in vitro performance of the resulting NPs were evaluated. Initially, high-throughput nanoprecipitation was employed for the εCL and δCL homopolymers to screen and establish important formulation parameters (organic solvent, polymer and surfactant concentration). Next, BRP-187-loaded PCL nanoparticles were prepared by batch nanoprecipitation and characterized using dynamic light scattering, scanning electron microscopy and UV-Vis spectroscopy to determine and to compare particle size, polydispersity, zeta potential, drug loading as well as the apparent enzymatic degradation as a function of the copolymer composition. Ultimately, NPs were examined for their potency in vitro in human polymorphonuclear leukocytes to inhibit the BRP-187 target 5-lipoxygenase-activating protein (FLAP). It was evident by Tukey's multi-comparison test that the degree of crystallinity of copolymers directly influenced their apparent enzymatic degradation and consequently their efficiency to inhibit the drug target.

SUBMITTER: Vollrath A

PROVIDER: S-EPMC8347491 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics.

Project description:The dual inhibitor of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E2 synthase-1 (mPGES-1), named BRP-187, represents a promising drug candidate due to its improved anti-inflammatory efficacy along with potentially reduced side effects in comparison to non-steroidal anti-inflammatory drugs (NSAIDs). However, BRP-187 is an acidic lipophilic drug and reveals only poor water solubility along with a strong tendency for plasma protein binding. Therefore, encapsulation in polymeric nanoparticles is a promising approach to enable its therapeutic use. With the aim to optimize the encapsulation of BRP-187 into poly(lactic-co-glycolic acid) (PLGA) nanoparticles, a single-phase herringbone microfluidic mixer was used for the particle preparation. Various formulation parameters, such as total flow rates, flow rate ratio, the concentration of the poly(vinyl alcohol) (PVA) as a surfactant, initial polymer concentration, as well as presence of a co-solvent on the final particle size distribution and drug loading, were screened for best particle characteristics and highest drug loading capacities. While the size of the particles remained in the targeted region between 121 and 259 nm with low polydispersities (0.05 to 0.2), large differences were found in the BRP-187 loading capacities (LC = 0.5 to 7.29%) and drug crystal formation during the various formulations.

| S-EPMC7699897 | biostudies-literature

Determining conformational order and crystallinity in polycaprolactone via Raman spectroscopy.

Project description:Raman spectroscopy is a popular method for non-invasive analysis of biomaterials containing polycaprolactone in applications such as tissue engineering and drug delivery. However there remain fundamental challenges in interpretation of such spectra in the context of existing dielectric spectroscopy and differential scanning calorimetry results in both the melt and semi-crystalline states. In this work, we develop a thermodynamically informed analysis method which utilizes basis spectra - ideal spectra of the polymer chain conformers comprising the measured Raman spectrum. In polycaprolactone we identify three basis spectra in the carbonyl region; measurement of their temperature dependence shows that one is linearly proportional to crystallinity, a second correlates with dipole-dipole interactions that are observed in dielectric spectroscopy and a third which correlates with amorphous chain behavior. For other spectral regions, e.g. C-COO stretch, a comparison of the basis spectra to those from density functional theory calculations in the all-trans configuration allows us to indicate whether sharp spectral peaks can be attributed to single chain modes in the all-trans state or to crystalline order. Our analysis method is general and should provide important insights to other polymeric materials.

| S-EPMC5557303 | biostudies-literature

Dual-Drug Containing Core-Shell Nanoparticles for Lung Cancer Therapy.

Project description:Late-stage diagnosis of lung cancer occurs ~95% of the time due to late manifestation of its symptoms, necessitating rigorous treatment following diagnosis. Existing treatment methods are limited by lack of specificity, systemic toxicity, temporary remission, and radio-resistance in lung cancer cells. In this research, we have developed a folate receptor-targeting multifunctional dual drug-loaded nanoparticle (MDNP) containing a poly(N-isopropylacrylamide)-carboxymethyl chitosan shell and poly lactic-co-glycolic acid (PLGA) core for enhancing localized chemo-radiotherapy to effectively treat lung cancers. The formulation provided controlled releases of the encapsulated therapeutic compounds, NU7441 - a potent radiosensitizer, and gemcitabine - an FDA approved chemotherapeutic drug for lung cancer chemo-radiotherapy. The MDNPs showed biphasic NU7441 release and pH-dependent release of gemcitabine. These nanoparticles also demonstrated good stability, excellent hemocompatibility, outstanding in vitro cytocompatibility with alveolar Type I cells, and dose-dependent caveolae-mediated in vitro uptake by lung cancer cells. In addition, they could be encapsulated with superparamagnetic iron oxide (SPIO) nanoparticles and visualized by MRI in vivo. Preliminary in vivo results demonstrated the low toxicity of these particles and their use in chemo-radiotherapy to effectively reduce lung tumors. These results indicate that MDNPs can potentially be used as nano-vehicles to provide simultaneous chemotherapy and radiation sensitization for lung cancer treatment.

| S-EPMC5643549 | biostudies-literature

Size and crystallinity in protein-templated inorganic nanoparticles.

Project description:Protein cages such as ferritins and virus capsids have been used as containers to synthesize a wide variety of protein-templated inorganic nanoparticles. While identification of the inorganic crystal phase has been successful in some cases, very little is known about the detailed nanoscale structure of the inorganic component. We have used pair distribution function analysis of total X-ray scattering to measure the crystalline domain size in nanoparticles of ferrihydrite, ?-Fe2O3, Mn3O4, CoPt, and FePt grown inside 24-meric ferritin cages from H. sapiens and P. furiosus. The material properties of these protein-templated nanoparticles are influenced by processes at a variety of length scales: the chemistry of the material determines the precise arrangement of atoms at very short distances, while the interior volume of the protein cage constrains the maximum nanoparticle size attainable. At intermediate length scales, the size of coherent crystalline domains appears to be constrained by the arrangement of crystal nucleation sites on the interior of the cage. Based on these observations, some potential synthetic strategies for the control of crystalline domain size in protein-templated nanoparticles are suggested.

| S-EPMC3756833 | biostudies-other

The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

Project description:Background and purposeLeukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis.Experimental approachWe analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis.Key resultsBRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels.Conclusions and implicationsBRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development.

| S-EPMC4055205 | biostudies-literature

Fabrication and characterization of polycaprolactone/chitosan nanofibers containing antibacterial agents of curcumin and ZnO nanoparticles for use as wound dressing

Project description:The potential of the nanoscale structure is utilized by electrospun nanofibers, which are promising materials for wound dressings. Here, we prepared wound dressings constituting polycaprolactone (PCL) and chitosan (CS). Curcumin (Cur) and zinc oxide nanoparticles (ZnO) as antibacterial agents were embedded in PCL/CS electrospun nanofibers and different properties including morphology, physicomechanical, interaction with water, antibacterial efficiency, and in vitro studies were investigated. SEM images confirmed the nanofibrous structure of samples with 100 ± 5 to 212 ± 25 nm in average diameter. Elemental analysis of nanofibers showed a good distribution of ZnO along nanofibers which not only caused decreasing in nanofiber diameter but also increased tensile strength of nanofibers up to 2.9 ± 0.5 MPa and with good elongation at break of 39 ± 2.9. ZnO nanoparticles also facilitated the interaction of nanofibers with water, and this led to the highest water vapor transition rate, which was equal to 0.28 ± 0.02 g cm−2 day−1. The sample containing 3 wt% Cur had the highest water uptake value (367 ± 15%) and the lowest water contact angle (78 ± 3.7°), although Cur has a hydrophobic nature. The release profile of Cur showed a two-stage release and the Peppas model predicted a non-fickian diffusion. Simultaneous incorporation of CS, ZnO, and Cur effectively inhibited bacterial growth. In addition, in vitro studies represented that high content of Cur decreases cell viability and cell attachment. The outcomes from the fabricated nanofibrous scaffolds demonstrated appropriate properties for application as a wound dressing.

| S-EPMC9539460 | biostudies-literature

Dual Effect of Chemo-PDT with Tumor Targeting Nanoparticles Containing iRGD Peptide.

Project description:Nanotechnology, including self-aggregated nanoparticles, has shown high effectiveness in the treatment of solid tumors. To overcome the limitations of conventional cancer therapies and promote therapeutic efficacy, a combination of PDT and chemotherapy can be considered an effective strategy for cancer treatment. This study presents the development of tumor-targeting polysialic acid (PSA) nanoparticles for chemo-PDT to increase the cellular uptake and cytotoxic effect in cancer cells. Chlorin e6 (Ce6), a photosensitizer, and the iRGD peptide (sequence; cCRGDKGPDC) were conjugated to the amine of N-deacetylated PSA. They generate reactive oxygen species (ROS), especially singlet oxygen (1O2), and target integrin αvβ3 on the cancer cell surface. To offer a chemotherapeutic effect, doxorubicin (Dox) was assembled into the core of hydrophobically modified PSA by connecting it with Ce6; this was followed by its sustained release from the nanoparticles. These nanoparticles are able to generate ROS under 633 nm visible-light irradiation, resulting in the strong cytotoxicity of Dox with anticancer effects in HCT116 cells. PSA nanoparticles with the dual effect of chemo-PDT improve conventional PDT, which has a poor ability to deliver photosensitizers to cancer cells. Using their combination with Dox chemotherapy, rapid removal of cancer cells can be expected.

| S-EPMC9959063 | biostudies-literature

Tunable Photoluminescence Properties of Cotton Fiber With Gradually Changing Crystallinity.

Project description:The alkali mercerizing process of semicrystalline cotton fiber (CF) is widely used in the printing and dyeing industry. The crystallinity change in the mercerizing process has been studied and certain laws have been obtained, but there is still a certain distance between the theoretical research results and the practical applications. CF is almost composed of cellulose, combined with the photoluminescence (PL) phenomenon of cellulose; herein, the varying crystallinity is correlated with its PL behavior after being treated with different concentrations of NaOH. In line with the characteristics of nonconventional luminogens, CF enjoys excitation-dependent emission and persistent room temperature phosphorescence (p-RTP) behavior. The emission spectra of all samples under the same excitation wavelength indicate that the change of CF crystallinity has a significant impact on its fluorescence and p-RTP emission. As the concentration of NaOH increases, the varying trend of quantum efficiency (QY) is consistent with the changed crystallinity of CF. Interestingly, the lifetime of p-RTP is exactly the opposite of the crystallinity change law. Clustering-triggered emission (CTE), crystallization-Induced Phosphorescence (CIP) mechanism, and the swelling due to hydrated sodium ions can reasonably explain these interesting photophysical processes, which also can be supported by theoretical calculations. The above studies have basically clarified the inherent law between the crystalline change of CF and the PL emission behavior during the alkali treatment process, which can be used as a theoretical reference for real-time monitoring of CF crystallinity changes using the spectral method in the actual cotton mercerizing process.

| S-EPMC9274137 | biostudies-literature

Dielectric Properties of Hybrid Polyethylene Composites Containing Cobalt Nanoparticles and Carbon Nanotubes.

Project description:Polymer composites with electrically conductive inclusions are intensively developed for microwave shielding applications, where lightweight and elastic coatings are necessary. In this paper, dielectric properties of hybrid polyethylene composites containing cobalt nanoparticles and multi-wall carbon nanotubes (MWCNT) were investigated in the wide frequency range of 20-40 GHz for electromagnetic shielding applications. The percolation threshold in the hybrid system is close to 6.95 wt% MWCNT and 0.56 Co wt%. Cobalt nanoparticles (up to highest investigated concentration 4.8 wt%) had no impact on the percolation threshold, and for the fixed total concentration of fillers, the complex dielectric permittivity is higher for composites with bigger MWCNT concentrations. Moreover, the microwave complex dielectric permittivity of composites with high concentration of fillers is quite high (for composites with 13.4 wt% MWCNT and 1.1 wt% Co ε' ≈ ε″ ≈ 20 at 30 GHz, it corresponds to microwave absorption 50% of 1 mm thickness plate); therefore, these composites are suitable for electromagnetic shielding applications.

| S-EPMC8912063 | biostudies-literature

Dual-cycle dielectrophoretic collection rates for probing the dielectric properties of nanoparticles.

Project description:A new DEP spectroscopy method and supporting theoretical model is developed to systematically quantify the dielectric properties of nanoparticles using continuously pulsed DEP collection rates. Initial DEP collection rates, that are dependent on the nanoparticle dielectric properties, are an attractive alternative to the crossover frequency method for determining dielectric properties. The new method introduces dual-cycle amplitude modulated and frequency-switched DEP (dual-cycle DEP) where the first collection rate with a fixed frequency acts as a control, and the second collection rate frequency is switched to a chosen value, such that, it can effectively probe the dielectric properties of the nanoparticles. The application of the control means that measurement variation between DEP collection experiments is reduced so that the frequency-switched probe collection is more effective. A mathematical model of the dual-cycle method is developed that simulates the temporal dynamics of the dual-cycle DEP nanoparticle collection system. A new statistical method is also developed that enables systematic bivariate fitting of the multifrequency DEP collection rates to the Clausius-Mossotti function, and is instrumental for determining dielectric properties. A Monte-Carlo simulation validates that collection rates improve estimation of the dielectric properties, compared with the crossover method, by exploiting a larger number of independent samples. Experiments using 200 nm diameter latex nanospheres suspended in 0.2 mS/m KCl buffer yield a nanoparticle conductivity of 26 mS/m that lies within 8% of the expected value. The results show that the dual-frequency method has considerable promise particularly for automated DEP investigations and associated technologies.

| S-EPMC3770930 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data