Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel.

ABSTRACT: Here, we report on the construction of biodegradable poly(ethylene oxide monomethyl ether) (MPEO)-b-poly(ε-caprolactone) (PCL) nanoparticles (NPs) having acid-labile (acyclic ketal group) linkage at the block junction. In the presence of acidic pH, the nanoassemblies were destabilized as a consequence of cleaving this linkage. The amphiphilic MPEO-b-PCL diblock copolymer self-assembled in PBS solution into regular spherical NPs. The structure of self-assemble and disassemble NPs were characterized in detail by dynamic (DLS), static (SLS) light scattering, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). The key of the obtained NPs is using them in a paclitaxel (PTX) delivery system and study their in vitro cytostatic activity in a cancer cell model. The acid-labile ketal linker enabled the disassembly of the NPs in a buffer simulating an acidic environment in endosomal (pH ~5.0 to ~6.0) and lysosomal (pH ~4.0 to ~5.0) cell compartments resulting in the release of paclitaxel (PTX) and formation of neutral degradation products. The in vitro cytotoxicity studies showed that the activity of the drug-loaded NPs was increased compared to the free PTX. The ability of the NPs to release the drug at the endosomal pH with concomitant high cytotoxicity makes them suitable candidates as a drug delivery system for cancer therapy.

SUBMITTER: Petrova SL

PROVIDER: S-EPMC8124141 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Light-triggered sequence-specific cargo release from DNA block copolymer-lipid vesicles.

Project description: Not available

| S-EPMC3563227 | biostudies-literature

Multi-stimuli sensitive amphiphilic block copolymer assemblies.

Project description:Stimuli-responsive polymers are arguably the most widely considered systems for a variety of applications in biomedical arena. We report here a novel triple stimuli sensitive block copolymer assembly that responds to changes in temperature, pH and redox potential. Our block copolymer design constitutes an acid-sensitive THP-protected HEMA as the hydrophobic part and a temperature-sensitive PNIPAM as the hydrophilic part with an intervening disulfide bond. The micellar properties and the release kinetics of the encapsulated guest molecule in response to one stimulus as well as combinations of stimuli have been evaluated. Responsiveness to combination of stimuli not only allows for fine-tuning the guest molecule release kinetics, but also provides the possibility of achieving location-specific delivery.

| S-EPMC2693022 | biostudies-literature

Agarose hydrogels embedded with pH-responsive diblock copolymer micelles for triggered release of substances.

Project description:Hybrid agarose hydrogels embedded with pH-responsive diblock copolymers micelles were developed to achieve functional hydrogels capable of stimulus-triggered drug release. Specifically, a well-defined poly(ethylene oxide) (PEO)-based diblock copolymer, PEO-b-poly(2-(N,N-diisopropylamino)ethyl methacrylate) (PEO(113)-b-PDPAEMA(31), where the subscripts represent the degrees of polymerization of two blocks), was synthesized by atom transfer radical polymerization. PDPAEMA is a pH-responsive polymer with a pKa value of 6.3. The PEO(113)-b-PDPAEMA(31) micelles were formed by a solvent-switching method, and their pH-dependent dissociation behavior was investigated by dynamic light scattering and fluorescence spectroscopy. Both studies indicated that the micelles were completely disassembled at pH = 6.40. The biocompatibility of PEO(113)-b-PDPAEMA(31) micelles was demonstrated by in vitro primary cortical neural culture. Hybrid agarose hydrogels were made by cooling 1.0 wt % agarose solutions that contained various amounts of PEO(113)-b-PDPAEMA(31) micelles at either 2 or 4 °C. Rheological measurements showed that the mechanical properties of gels were not significantly adversely affected by the incorporation of diblock copolymer micelles with a concentration as high as 5.0 mg/g. Using Nile Red as a model hydrophobic drug, its incorporation into the core of diblock copolymer micelles was demonstrated. Characterized by fluorescent spectroscopy, the release of Nile Red from the hybrid hydrogel was shown to be controllable by pH due to the responsiveness of the block copolymer micelles. Based on the prominent use of agarose gels as scaffolds for cell transplantation for neural repair, the hybrid hydrogels embedded with stimuli-responsive block copolymer micelles could allow the controlled delivery of hydrophobic neuroprotective agents to improve survival of transplanted cells in tune with signals from the surrounding pathological environment.

| S-EPMC3773184 | biostudies-literature

DNA/amphiphilic block copolymer nanospheres promote low-dose DNA vaccination.

Project description:Intramuscular (i.m.) DNA vaccination induces strong cellular immune responses in the mouse, but only at DNA doses that cannot be achieved in humans. Because antigen expression is weak after naked DNA injection, we screened five nonionic block copolymers of poly(ethyleneoxide)-poly(propyleneoxide) (PEO-PPO) for their ability to enhance DNA vaccination using a beta-galactosidase (betaGal) encoding plasmid, pCMV-betaGal, as immunogen. At a high DNA dose, formulation with the tetrafunctional block copolymers 304 (molecular weight [MW] 1,650) and 704 (MW 5,500) and the triblock copolymer Lutrol (MW 8,600) increased betaGal-specific interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) responses 2-2.5-fold. More importantly, 704 allowed significant reductions in the dose of antigen-encoding plasmid. A single injection of 2 microg pCMV-betaGal with 704 gave humoral and ELISPOT responses equivalent to those obtained with 100 microg naked DNA and conferred protection in tumor vaccination models. However, 704 had no adjuvant properties for betaGal protein, and immune responses were only elicited by low doses of pCMV-betaGal formulated with 704 if noncoding carrier DNA was added to maintain total DNA dose at 20 microg. Overall, these results show that formulation with 704 and carrier DNA can reduce the dose of antigen-encoding plasmid by at least 50-fold.

| S-EPMC2835232 | biostudies-literature

Poly(ethylene oxide)-block-polyphosphoester-graft-paclitaxel conjugates with acid-labile linkages as a pH-sensitive and functional nanoscopic platform for paclitaxel delivery.

Project description:There has been an increasing interest to develop new types of stimuli-responsive drug delivery vehicles with high drug loading and controlled release properties for chemotherapeutics. An acid-labile poly(ethylene oxide)-block-polyphosphoester-graft-PTX drug conjugate (PEO-b-PPE-g-PTX G2) degradable, polymeric paclitaxel (PTX) conjugate containing ultra-high levels of PTX loading is improved significantly, in this second-generation development, which involves connection of each PTX molecule to the polymer backbone via a pH-sensitive ?-thiopropionate linkage. The PEO-b-PPE-g-PTX G2 forms well-defined nanoparticles in an aqueous solution, by direct dissolution into water, with a number-averaged hydrodynamic diameter of 114 ± 31 nm, and exhibits a PTX loading capacity as high as 53 wt%, with a maximum PTX concentration of 0.68 mg mL(-1) in water (vs 1.7 ?g mL(-1) for free PTX). The PEO-b-PPE-g-PTX G2 shows accelerated drug release under acidic conditions (?50 wt% PTX released in 8 d) compared with neutral conditions (?20 wt% PTX released in 8 d). Compared to previously reported polyphosphoester-based PTX drug conjugates, PEO-b-PPE-g-PTX G1 without the ?-thiopropionate linker, the PEO-b-PPE-g-PTX G2 shows pH-triggered drug release property and 5- to 8-fold enhanced in vitro cytotoxicity against two cancer cell lines.

| S-EPMC3938983 | biostudies-literature

Enzyme and pH dual responsive linear-dendritic block copolymer micelles based on a phenylalanyl-lysine motif and peripherally ketal-functionalized dendron as potential drug carriers.

Project description:Stimuli-responsive linear-dendritic block copolymers (LDBCs) have attracted significant research attention as novel drug carriers. We report here three generations of new enzyme and pH dual responsive linear-dendritic block copolymers (LDBCs) with a phenylalanyl-lysine (Phe-Lys) dipeptide linking hydrophilic linear poly(N-vinylpyrrolidone) (PNVP) and a hydrophobic peripherally ketal-functionalized dendron derived from 2,2'-bis(hydroxymethyl)propionic acid (bis-MPA). The LDBCs are synthesized via a combination of interchange of xanthates/reversible addition-fragmentation chain transfer (MADIX/RAFT) polymerization of N-vinylpyrrolidone (NVP) and "chain-first" strategy. Their structures are confirmed by 1H NMR spectra. The gel permeation chromatograph (GPC) analysis revealed that the LDBCs have a narrow molecular weight distribution (PDI ≤ 1.25). The amphiphilic LDBCs can self-assemble into spherical nanomicelles in aqueous solution. The presence of enzyme or/and the change of pH cause disassembly of micelles to release encapsulated cargos. The release rates of the guest molecules are faster in buffer solution at pH 5.0 than those upon the addition of the activating enzyme and can be fine-tuned by changing the generation of bis-MPA dendrons. The combination of enzyme and pH dual stimuli results in significantly accelerated and more complete release of the loaded hydrophobic guests. The cell viability assay confirmed the favorable biocompatibility until the LDBC micelle concentration reached 800 μg mL-1. These results indicate that the LDBCs can be considered as a good candidate for targeting drug delivery.

| S-EPMC10360044 | biostudies-literature

Amphiphilic Block Copolymers Bearing Hydrophobic γ-Tocopherol Groups with Labile Acetal Bond.

Project description:High concentrations of γ-tocopherol (γTCP) tend to show antioxidant, anti-inflammatory, and anticancer effects. In this study, we prepared polymer micelles under acidic conditions with a controlled release of γTCP due to the decomposition of pendant acetal bonds. First, a precursor diblock copolymer composed of poly(ethylene glycol) (PEG) and acrylic acid (AA) was prepared. This was followed by the synthesis of an amphiphilic diblock copolymer (PEG54-P(AA/VE6/γTCP29)140), incorporated into hydrophobic γTCP pendant groups attached to the main chain through an acetal bond. The prepared PEG54-P(AA/VE6/γTCP29)140 was further dispersed in water to form polymer micelles composed of hydrophobic cores that were generated from a hydrophobic block containing γTCPs and hydrophilic shells on the surface. Under acidic conditions, γTCP was then released from the core of the polymer micelles due to the decomposition of the pendant acetal bonds. In addition, polymer micelles swelled under acidic conditions due to hydration of the core.

| S-EPMC7023524 | biostudies-literature

A simple way to enhance Doxil® therapy: drug release from liposomes at the tumor site by amphiphilic block copolymer.

Project description:The antitumor efficacy of Doxil® is hindered by the poor release of the active drug from the liposome at the tumor sites. This study investigates a possibility to enhance drug release from the liposomes and increase therapeutic efficacy of Doxil® by administering Pluronic block copolymers once the liposomal drug accumulates in the tumor sites. In our study, the fluorescence de-quenching experiments were designed to investigate the drug release from liposome by Pluronic P85. MTT cytotoxicity assay and confocal microscopy images were carried out to determine whether Pluronic P85 could facilitate release of Dox from Doxil®. Anti-tumor growth and distribution of drug were evaluated when Pluronic P85 was injected 1h, 48h, or 96h after the Doxil® administration in A2780 human ovarian cancer xenografts. Addition of Pluronic P85 resulted in release of Dox from the liposomes accompanied with significant increases of Dox delivery and cytotoxic effect in cancer cells. The greatest anti-tumor effect of single injection of Doxil® was achieved when Pluronic P85 was administered 48h after Doxil®. The confocal tile scanning images of tumor section showed that copolymer treatment induced the release of the drug in the tumors from the vessels regions to the bulk of the tumor. No release of the drug remaining in circulation was observed. Our study has demonstrated a simple approach for localized release of Dox from liposome by Pluronic P85 at the tumor site, which was therapeutically beneficial.

| S-EPMC3661699 | biostudies-literature

Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery.

Project description:To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

| S-EPMC4554410 | biostudies-literature

Film Confinement Induced "Jump-Percolation" Wetting Transition in Amphiphilic Block Copolymer Films.

Project description:We report a first-order like sharp surface wettability transition with varying film thickness dependent morphology in cast films of an amphiphilic triblock copolymer. Films composed of poly(2-(N-ethylperfluorooctanesulfonamido) ethyl methyl acrylate), poly(FOSM), and poly(N,N'-dimethyl acrylamide), poly(DMA), with thickness (h) in the transition-range, 200 < h < 300 nm, exhibited an abrupt hydrophobic to hydrophilic dynamic water contact angle transition. After an induction time, ti ≈ 40 to 180 s, water contact angle varied as θc ≈ 116° to 40° with an ultrafast contact angle decay time constant, [Formula: see text] ≈ -18°/s. This behavior is a result of competing heterogeneous and antagonistic effects of bumpy poly(DMA) wetting domains against a nonwetting planar poly(FOSM) background, with a "jump percolation" wetting transition when the poly(DMA) domain density reaches unity. Outside of this film thickness range, relatively shallow decreasing water contact angle gradients were observed with a monotonically increasing poly(DMA) domain area coverage with increasing film thickness in the overall range of 40 nm (hydrophobic, θc ≈ 118°) < h < 500 nm (hydrophilic, θc ≈ 8°). The optical diffuse reflectance properties of these rough surfaces exhibit an onset of diffuse reflectance maxima correlated to the transition morphology film thickness.

| S-EPMC11240273 | 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