Hydrogen-bonded multilayer of pH-responsive polymeric micelles with tannic acid for surface drug delivery.
Ontology highlight
ABSTRACT:
SUBMITTER: Kim BS
PROVIDER: S-EPMC3965301 | biostudies-literature | 2009 Jul
REPOSITORIES: biostudies-literature
Publications
Hydrogen-bonded multilayer of pH-responsive polymeric micelles with tannic acid for surface drug delivery.
Kim Byeong-Su BS Lee Hyung-Il HI Min Yunhong Y Poon Zhiyong Z Hammond Paula T PT
Chemical communications (Cambridge, England) 20090616 28
We report the design of a platform for the delivery of hydrophobic drugs conjugated to block copolymer micelles via pH-responsive linkage that are assembled within hydrogen-bonded polymer multilayer thin films. ...[more]
Similar Datasets
Project description:It is of great significance to study the structure property and self-assembly of amphiphilic block copolymer in order to effectively and efficiently design and prepare drug delivery systems. In this work, dissipative particle dynamics (DPD) simulation method was used to investigate the structure property and self-assembly ability of pH-responsive amphiphilic block copolymer poly(methyl methacrylate-co-methacrylic acid)-b-poly(aminoethyl methacrylate) (poly(MMA-co-MAA)-b-PAEMA). The effects of different block ratios (hydrophilic PAEMA segment and pH-sensitive PMAA segment) in copolymer on self-assembly and drug loading capacity including drug distribution were extensively investigated. The increase of hydrophilic PAEMA facilitated the formation of a typical core-shell structure as well as a hydrophobic PMAA segment. Furthermore, the optimal drug-carrier ratio was confirmed by an analysis of the drug distribution during the self-assembly process of block copolymer and model drug Ibuprofen (IBU). In addition, the drug distribution and nanostructure of IBU-loaded polymeric micelles (PMs) self-assembled from precise block copolymer (PMMA-b-PMAA-b-PAEMA) and block copolymer (poly(MMA-co-MAA)-b-PAEMA) with random pH-responsive/hydrophobic structure were evaluated, showing that almost all drug molecules were encapsulated into a core for a random copolymer compared to the analogue. The nanostructures of IBU-loaded PMs at different pH values were evaluated. The results displayed that the nanostructure was stable at pH < pKa and anomalous at pH > pKa which indicated drug release, suggesting that the PMs could be used in oral drug delivery. These findings proved that the amphiphilic block copolymer P(MMA30-co-MAA33)-b-PAEMA38 with random structure and pH-sensitivity might be a potential drug carrier. Moreover, DPD simulation shows potential to study the structure property of PMs self-assembled from amphiphilic block copolymer.
| S-EPMC6956019 | biostudies-literature
Project description:β-Lapachone (β-lap), a novel anticancer agent, is bioactivated by NADP(H):quinone oxidoreductase 1 (NQO1), an enzyme over-expressed in numerous tumors, including lung, pancreas, breast, and prostate cancers. Fast renal clearance and methemaglobinemia / hemolytic side-effects from the clinical formulation (β-lap-hydroxyl propyl-β-cyclodextrin complex) hindered its clinical translation. Here, we investigated a dual model pH responsive polymers for β-lap delivery. Three pH-sensitive linkages, including acylhydrazone, ketal and imine bonds for β-lap prodrug syntheses result in an aryl imine linkage the most optimal linkage. The conversion to β-lap was 2.8%, 4.5% and 100% at pH 7.4, 6.5 and 5.0 in 8 h, respectively. β-lap aryl imine prodrug conjugated ultra pH-sensitive (UPS) polymer reached high β-lap loading density (8.3%) and exhibited dual-stages responsiveness to pH variation. In pHs under pHt, at stage I, micelle immediately dissociation and subsequently entering stage II, micelles start quickly release β-lap. In vitro release study showed that the micelles constantly release β-lap (14.9 ± 0.1%) at pHs above pHt in 72 h, whereas boosted release of β-lap (79.4 ± 1.2%) at pH 5.0. Micelle intracellular distribution predominantly in the lysosome organelle guaranteed their pH responsive dissociation and subsequently β-lap controlled release. The M-P micelles retained NQO1-dependent cytotoxicity in A549 lung cancer cells, similar to free drug in both efficacy and mechanism of cell death. The lysosome-oriented dual-stage ultra pH responsive β-lap prodrug micelles potentially offer an alternative nanotherapeutic strategy for lung, as well as other NQO1+ cancer therapies.
| S-EPMC5452003 | biostudies-literature
Project description:Messenger RNA (mRNA) is emerging as a promising therapeutic modality for a variety of diseases. Because of the fragility and limited intracellular access of mRNA, the development of delivery technologies is essential for promoting the applicability of mRNA-based treatments. Among effective nanocarriers, polymeric micelles loading mRNA by polyion complex (PIC) formation with block catiomers have the potential to meet the delivery needs. Since PICs are relatively unstable in in vivo settings, herein, we constructed mRNA-loaded micelles having pH-responsive cross-linked cores by complexing mRNA with cis-aconitic anhydride-modified poly(ethylene glycol)-poly(l-lysine) (PEG-pLL(CAA)) block copolymers. The micelles were stable at physiological pH (pH 7.4) but achieved the complete release of the mRNA at endosomal pH (pH 5.5-4.5). The cross-linking also enhanced the stability of the micelles against disassembly from polyanions and protected the loaded mRNA from degradation by nucleases. Thus, the cross-linked micelles increased the delivery of mRNA to cancer cells, promoting protein expression both in vitro and in vivo. Our results highlight the potential of PEG-pLL(CAA)-based micelles for mRNA delivery.
| S-EPMC9231146 | biostudies-literature
Project description:Stimuli-responsive polymeric micelles (PMs) have shown great potential in drug delivery and controlled release in cancer chemotherapy. Herein, inspired by the features of the tumor microenvironment, we developed dual pH/redox-responsive mixed PMs which are self-assembled from two kinds of amphiphilic diblock copolymers (poly(ethylene glycol) methyl ether-b-poly(?-amino esters) (mPEG-b-PAE) and poly(ethylene glycol) methyl ether-grafted disulfide-poly(?-amino esters) (PAE-ss-mPEG)) for anticancer drug delivery and controlled release. The co-micellization of two copolymers is evaluated by measurement of critical micelle concentration (CMC) values at different ratios of the two copolymers. The pH/redox-responsiveness of PMs is thoroughly investigated by measurement of base dissociation constant (pKb) value, particle size, and zeta-potential in different conditions. The PMs can encapsulate doxorubicin (DOX) efficiently, with high drug-loading efficacy. The DOX was released due to the swelling and disassembly of nanoparticles triggered by low pH and high glutathione (GSH) concentrations in tumor cells. The in vitro results demonstrated that drug release rate and cumulative release are obviously dependent on pH values and reducing agents. Furthermore, the cytotoxicity test showed that the mixed PMs have negligible toxicity, whereas the DOX-loaded mixed PMs exhibit high cytotoxicity for HepG2 cells. Therefore, the results demonstrate that the dual pH/redox-responsive PMs self-assembled from PAE-based diblock copolymers could be potential anticancer drug delivery carriers with pH/redox-triggered drug release, and the fabrication of stimuli-responsive mixed PMs could be an efficient strategy for preparation of intelligent drug delivery platform for disease therapy.
| S-EPMC6523239 | biostudies-literature
Project description:Stimuli-responsive drug delivery systems (DDSs) are expected to realize site-specific drug release and kill cancer cells selectively. In this study, a pH-responsive micelle was designed utilizing the pH-sensitivity of borate bonds formed between dopamine and boronic acid. First, methyl (polyethylene glycol)-block-polycaprolactone (mPEG-PCL) was conjugated with 4-cyano-4-(thiobenzoylthio)pentanoic acid (CTP) to obtain a macroinitiator. Two different segments poly(dopamine methacrylamide) (PDMA) and poly(vinylphenylboronic acid) (PVBA) were then grafted to the end of mPEG-PCL. Two triblock copolymers, mPEG-PCL-PDMA and mPEG-PCL-PVBA, were then obtained by reversible addition-fragmentation transfer (RAFT) polymerization. These copolymers and their mixture self-assembled in aqueous solution to form micelles that were able to load hydrophobic anticancer drug doxorubicin (DOX). These two-component micelles were found to be pH-sensitive, in contrast to the one-component micelles. Furthermore, MTT studies showed that the micelles were almost nontoxic. The DOX-loaded micelles showed cytotoxicity equivalent to that of DOX at high concentration. In vivo antitumor experiments showed that this pH-sensitive polymeric micellar system had an enhanced therapeutic effect on tumors. These two-component boronate-based pH micelles are universally applicable to the delivery of anticancer drugs, showing great potential for cancer therapy.
| S-EPMC7054969 | biostudies-literature
Project description:Polymeric micelles (PMs) have been widely investigated as nanocarriers for drug delivery and cancer treatments due to their excellent physicochemical properties, drug loading and release capacities, facile preparation methods, biocompatibility, and tumor targetability. They can be easily engineered with various functional moieties to further improve their performance in terms of bioavailability, circulation time, tumor specificity, and anticancer activity. The stimuli-sensitive PMs capable of responding to various extra- and intracellular biological stimuli (eg, acidic pH, altered redox potential, and upregulated enzyme), as well as external artificial stimuli (eg, magnetic field, light, temperature, and ultrasound), are considered as "smart" nanocarriers for delivery of anticancer drugs and/or imaging agents for various therapeutic and diagnostic applications. In this article, the recent advances in the development of stimuli-responsive PMs for drug delivery, imaging, and cancer therapy are reviewed. The article covers the generalities of stimuli-responsive PMs with a focus on their major delivery strategies and newly emerging technologies/nanomaterials, discusses their drawbacks and limitations, and provides their future perspectives.
| S-EPMC5965378 | biostudies-literature
Project description:To prepare mixed polymeric micelles that can carry two different drugs, doxorubicin (DOX) and 17-hydroxyethylamino-17-demethoxygeldanamycin (GDM-OH), for combination cancer chemotherapy.The pH-sensitive micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers to which either DOX or GDM-OH is conjugated through acid-labile hydrazone bond (individual micelles). Mixed micelles were formed not only by simply mixing two different individual micelles in aqueous solutions (aqueous mixed micelles) but also by evaporating organic solvents from the organic/aqueous mixed solvents in which two block copolymers possessing different drugs were dissolved homogeneously (organic mixed micelles). Particle size measurements, pH-dependent drug release tests, cytotoxicity assays and western blot analysis were subsequently conducted.Individual and aqueous/organic mixed micelles showed clinically relevant particle size (<100 nm) and pH-dependent drug release patterns. Mixed polymer micelles suppress cancer cell growth effectively in a drug concentration, mixing method and schedule-dependent way.Combination chemotherapy using polymeric micelles seems to minimize a schedule-dependent change in combination drug efficacy in comparison to drug combination using DMSO formulations.
| S-EPMC5568702 | biostudies-other
Project description:Low tumor specificity and multidrug resistance (MDR) remain challenging for many anticancer drugs. In this study, the micelles assembled by a matrix metalloproteinase 2 (MMP2)-sensitive self-assembling efflux inhibitor (PEG2k-pp-PE) were developed and evaluated in various cancer models. In vitro, the PEG2k-pp-PE micelles enhanced the cellular uptake and tissue penetration and sensitized the cancers to drug treatments in MDR cancer cells and their three-dimensional multicellular spheroids. Their efflux inhibitory capability was comparable to those of the well-known small-molecule P-glycoprotein (P-gp) inhibitor and polymeric P-gp inhibitor. In vivo, the PEG2k-pp-PE micelles could specifically and effectively deliver the loaded cargoes to the tumor, as evidenced by the enhanced drug accumulation and prolonged drug retention in the tumor tissue, resulting in the improved anticancer activity. Our results suggest that the PEG2k-pp-PE micelles may have great potential to be a simple but multifunctional nanocarrier for concurrent tumor-targeted drug delivery and sensitization of resistant cancers.
| S-EPMC6599579 | biostudies-literature
Project description:Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance. We design three ionizable oligo-mers (IOs) that, with PLA-PEG, form Ionizable Polymeric Micelles (IPMs), a potential siRNA delivery system, which can achieve lysosomal escape. FAPi-modified IPMs (FAPi-IPMs) show higher targeting of activated hepatic stellate cells (HSCs) compared to hepatocytes, silencing both HSP47 and HMGB1, reducing collagen secretion and liv-er inflammation, effectively treating fibrosis. Moreover, IPMs and FAPi-IPMs mitigate accelerated blood clearance and produce fewer PEG antibodies than LNPs. Unlike LNPs, which adsorb apolipoprotein E (ApoE), IPMs and FAPi-IPMs show minimal apolipoprotein adsorption, differentiating their targeting effects from LNPs. In conclu-sion, IPMs represent an alternative nucleic acid delivery system with superior targeting and reduced immune clearance.
2024-11-21 | PXD057444 | Pride
Project description:Biodegradable nanoparticles (NPs) have shown great promise as intracellular imaging probes, nanocarriers and drug delivery vehicles. In this study, we designed and prepared amphiphilic cellulose derivatives via Schiff base reactions between 2,3-dialdehyde cellulose (DAC) and amino compounds. Polymeric NPs were facilely fabricated via the self-assembly of the as-synthesized amphiphilic macromolecules. The size distribution of the obtained NPs can be tuned by changing the amount and length of the grafted hydrophobic side-chains. Anticancer drugs (DOX) were encapsulated in the NPs and the drug-loaded NPs based on cellulose derivatives were stable in neutral and alkaline environments for at least a month. They rapidly decomposed with the efficient release of the drug in acidic tumor microenvironments. These drug-loaded NPs have the potential for application in cancer treatment.
| S-EPMC9049203 | biostudies-literature