The core-inversible micelles for hydrophilic drug delivery.
Ontology highlight
ABSTRACT:
SUBMITTER: Huang W
PROVIDER: S-EPMC3733992 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Publications
The core-inversible micelles for hydrophilic drug delivery.
Huang Wenzhe W Shi Changying C Shao Yu Y Lam Kit S KS Luo Juntao J
Chemical communications (Cambridge, England) 20130701 59
A unique core-inversible micelle (CIM) was formed via PEG(5k)CA8 for hydrophilic drug delivery. An amyloid-fibril-inhibiting water-soluble molecule, congo red (CR), has been loaded into the hydrophilic core of CIMs. The targeting folate-CIMs significantly enhanced the intracellular delivery of hydrophilic CR in a folate receptor-expressing cell line. ...[more]
Similar Datasets
Project description:In this study, diselenide (Se-Se) and disulfide (S-S) redox-responsive core-cross-linked (CCL) micelles were synthesized using poly(ethylene oxide)2k-b-poly(furfuryl methacrylate)1.5k (PEO2k-b-PFMA1.5k), and their redox sensitivity was compared. A single electron transfer-living radical polymerization technique was used to prepare PEO2k-b-PFMA1.5k from FMA monomers and PEO2k-Br initiators. An anti-cancer drug, doxorubicin (DOX), was incorporated into PFMA hydrophobic parts of the polymeric micelles, which were then cross-linked with maleimide cross-linkers, 1,6-bis(maleimide) hexane, dithiobis(maleimido) ethane and diselenobis(maleimido) ethane via Diels-Alder reaction. Under physiological conditions, the structural stability of both S-S and Se-Se CCL micelles was maintained; however, treatments with 10 mM GSH induced redox-responsive de-cross-linking of S-S and Se-Se bonds. In contrast, the S-S bond was intact in the presence of 100 mM H2O2, while the Se-Se bond underwent de-crosslinking upon the treatment. DLS studies revealed that the size and PDI of (PEO2k-b-PFMA1.5k-Se)2 micelles varied more significantly in response to changes in the redox environment than (PEO2k-b-PFMA1.5k-S)2 micelles. In vitro release studies showed that the developed micelles had a lower drug release rate at pH 7.4, whereas a higher release was observed at pH 5.0 (tumor environment). The micelles were non-toxic against HEK-293 normal cells, which revealed that they could be safe for use. Nevertheless, DOX-loaded S-S/Se-Se CCL micelles exhibited potent cytotoxicity against BT-20 cancer cells. Based on these results, the (PEO2k-b-PFMA1.5k-Se)2 micelles can be more sensitive drug carriers than (PEO2k-b-PFMA1.5k-S)2 micelles.
| S-EPMC10144204 | biostudies-literature
Project description:Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ?-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic.
| S-EPMC4201986 | biostudies-literature
Project description:Amphiphilic block polypeptides can self-assemble into a range of nanostructures in solution, including micelles and vesicles. Our group has recently described the capacity of recombinant amphiphilic diblock copolypeptides to form highly stable micelles. In this report, we demonstrate the utility of protein nanoparticles to serve as a vehicle for controlled drug delivery. Drug-loaded micelles were produced by encapsulating dipyridamole as a model hydrophobic drug with anti-inflammatory activity. Murine studies confirmed the capacity of drug-loaded protein micelles to limit the in vivo recruitment of neutrophils in response to an inflammatory stimulus.
| S-EPMC3226903 | biostudies-literature
Project description:The structure of nanospheres with a crystalline core and an amorphous diffuse shell was investigated by small-angle neutron scattering (SANS), small-, medium-, and wide-angle X-ray scattering (SAXS, MAXS and WAXS), and differential scanning calorimetry (DSC). Nanospheres, 28 to 35 nm in diameter, were prepared from a triblock copolymer with poly(ethylene glycol) (PEG) hydrophilic end-blocks and oligomers of alternating desaminotyrosyl-tyrosine octyl ester (DTO) and suberic acid (SA) as the central hydrophobic block. In the lyophilized nanospheres, the diffraction patterns show that the PEG shell is ∼10 nm in thickness and crystalline, and the hydrophobic core is ∼10 nm in diameter with a smectic liquid crystalline texture. In aqueous dispersions, the hydrated PEG forms an amorphous shell, but the crystalline phase in the core persists at concentrations down to 1 mg ml-1 as evidenced by the sharp MAXS diffraction peak at a d-spacing of 24.4 Å and a melting endotherm at 40 °C. As the dispersion is diluted (<1 mg ml-1), the core becomes less ordered, and its diameter decreases by 50% even though the overall size of the nanosphere remains essentially unchanged. It is likely that below a critical concentration, intermixing of hydrophobic segments with the PEG segments reduces the size and the crystallinity of the core. At these concentrations, the PEG corona forms a eutectic with water. The mechanisms by which the concentration of the dispersion influences the structure of the nanospheres, and consequently their drug-release characteristics, are discussed.
| S-EPMC5929128 | 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:To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS3350-GPLGVRGDG-DOX&DOX micelles, where TPGS3350 is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS3350-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS3350-GPLGVRG-DOX&DOX micelles and TPGS3350-DOX&DOX micelles. During in vivo studies, TPGS3350-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS3350-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications.
| S-EPMC9456463 | biostudies-literature
Project description:Nanoparticle drug carriers hold potential to improve current cancer therapy by delivering payload to the tumor environment and decreasing toxic side effects. Challenges in nanotechnology drug delivery include plasma instability, site-specific delivery, and relevant biomarkers. We have developed a triblock polymer comprising a hydroxamic acid functionalized center block that chelates iron to form a stabilized micelle that physically entraps chemotherapeutic drugs in the hydrophobic core. The iron-imparted stability significantly improves the integrity of the micelle and extends circulation pharmacokinetics in plasma over that of free drug. Furthermore, the paramagnetic properties of the iron-crosslinking exhibits contrast in the tumors for imaging by magnetic resonance. Three separate nanoparticle formulations demonstrate improved anti-tumor efficacy in xenograft models and decreased toxicity. We report a stabilized polymer micelle that improves the tolerability and efficacy of chemotherapeutic drugs, and holds potential for non-invasive MRI to image drug delivery and deposition in the tumor.
| S-EPMC5451294 | 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:Polyion complex (PIC) micelles have gained an increasing interest, mainly as promising nano-vehicles for the delivery of various hydrophilic charged (macro)molecules such as DNA or drugs to the body. The aim of the present study is to construct novel functional PIC micelles bearing cell targeting ligands on the surface and to evaluate the possibility of a hydrophobic drug encapsulation. Initially, a pair of functional oppositely charged peptide-based hybrid diblock copolymers were synthesized and characterized. The copolymers spontaneously co-assembled in water into nanosized PIC micelles comprising a core of a polyelectrolyte complex between poly(L-aspartic acid) and poly(L-lysine) and a biocompatible mixed shell of disaccharide-modified poly(ethylene glycol) and poly(2-hydroxyethyl methacrylate). Depending on the molar ratio between the oppositely charged groups, PIC micelles varying in surface charge were obtained and loaded with the natural hydrophobic drug curcumin. PIC micelles' drug loading efficiency, in vitro drug release profiles and antioxidant activity were evaluated. The preliminary results indicate that PIC micelles can be successfully used as carriers of hydrophobic drugs, thus expanding their potential application in nanomedicine.
| S-EPMC9000450 | biostudies-literature
Project description:Natural polymers provide a better alternative to synthetic polymers in the domain of drug delivery systems (DDSs) because of their renewability, biocompatibility, and low immunogenicity; therefore, they are being studied for the development of bulk/nanoformulations. Likewise, current methods for engineering natural polymers into micelles are in their infancy, and in-depth studies are required using natural polymers as controlled DDSs. Accordingly, in our present study, a new micellar DDS was synthesized using ethyl cellulose (EC) grafted with polyethylene glycol (PEG); it was characterized, its properties, cell toxicity, and hemocompatibility were evaluated, and its drug release kinetics were demonstrated using doxorubicin (DOX) as a model drug. Briefly, EC was grafted with PEG to form the amphiphilic copolymers EC-PEG1 and EC-PEG2 with varying PEG concentrations, and nano-micelles were prepared with and without the drug (DOX) via a dialysis method; the critical micelle concentrations (CMCs) were recorded to be 0.03 mg mL-1 and 0.00193 mg mL-1 for EC-PEG1 and EC-PEG2, respectively. The physicochemical properties of the respective nano-micelles were evaluated via various characterization techniques. The morphologies of the nano-micelles were analyzed via transmission electron microscopy (TEM), and the average size of the nano-micelles was recorded to be ∼80 nm. In vitro, drug release studies were done for 48 h, where 100% DOX release was recorded at pH 5.5 and 52% DOX release was recorded at pH 7.4 from the micelles. In addition, cytotoxicity studies suggested that DOX-loaded micelles were potent in killing MDA-MB-231 and MCF-7 cancer cells, and the blank micelles were non-toxic toward cancerous and normal cells. A cellular uptake study via fluorescence microscopy indicated the internalization of DOX-loaded micelles by cancer cells, delivering the DOX into the cellular compartments. Based on these studies, we concluded that the developed material should be studied further via in vivo studies to understand its potential as a controlled DDS to treat cancer.
| S-EPMC9041117 | biostudies-literature