Preparation of polyion complex micelles from poly(ethylene glycol)-block-polyions

Bayó‐Puxán, Núria; Dufresne, Marie-Hélène; Felber, Arnaud E.; Castagner, Bastien; Leroux, Jean‐Christophe

doi:10.1016/j.jconrel.2011.07.027

Cited by 31 publications

(22 citation statements)

References 45 publications

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“…In the design of nucleic acid delivery vectors, a multitude of efforts has been made to overcome many of the extra- and intracellular obstacles by incorporation of hydrophilic poly(ethylene glycol) moieties to suppress the adsorption of serum proteins, 10–12 membrane destabilizing and pH-sensitive polymers for endosomal escape, 7,13–15 targeting ligands 16–18 or covalent crosslinking for stabilization against counter polyion exchange. 8,19–21 However, only a few studies has been focused on minimizing the overall toxicity of cationic carriers by integration of degradability and evaluating their long term fate.…”

Section: Introductionmentioning

confidence: 99%

Degradable Cationic Shell Cross-Linked Knedel-like Nanoparticles: Synthesis, Degradation, Nucleic Acid Binding, and in Vitro Evaluation

et al. 2013

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In this work, degradable cationic shell crosslinked knedel-like (deg-cSCK) nanoparticles were developed as an alternative platform to replace similar non-degradable cSCK nanoparticles that have been utilized for nucleic acids delivery. An amphiphilic diblock copolymer poly(acrylamidoethylamine)90-block-poly(DL-lactide)40 (PAEA90-b-PDLLA40) was synthesized, self-assembled in aqueous solution and shell crosslinked using a hydrolyzable crosslinker to afford deg-cSCKs with an average core diameter of 45 ± 7 nm. These nanoparticles were fluorescently labeled for in vitro tracking. The enzymatic- and hydrolytic-degradability, siRNA binding affinity, cell uptake and cytotoxicity of the deg-cSCKs were evaluated. Esterase-catalyzed hydrolysis of the nanoparticles resulted in the degradation of ca. 24% of the PDLLA core into lactic acid within 5 d, as opposed to only ca. 9% degradation from aqueous solutions of the deg-cSCK nanoparticles in the absence of enzyme. Cellular uptake of deg-cSCKs was efficient, while exhibiting low cytotoxicity with LD50 values of ca. 90 μg/mL and 30 μg/mL in RAW 264.7 mouse macrophages and MLE 12 cell lines, respectively, ca. 5–6-fold lower than the cytotoxicity observed for non-degradable cSCK analogs. Additionally, deg-cSCKs were able to complex siRNA at an N/P ratio as low as 2, and were efficiently able to facilitate cellular uptake of the complexed nucleic acids.

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Section: Introductionmentioning

confidence: 99%

Degradable Cationic Shell Cross-Linked Knedel-like Nanoparticles: Synthesis, Degradation, Nucleic Acid Binding, and in Vitro Evaluation

et al. 2013

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“…This electrostatic complex has a core-shell structure, which is termed as polyion complex micelle (PCM). 24,25 Unlike common micelles that are formed only with amphiphilic block copolymers, electronic segments are conjugated onto the lipophilic terminus of the block copolymers and the PCM is formed with a complex of cationic and anionic segments through electrostatic interactions. Through this unique method, the synthesized PCM will not only be more stable than the normal PMs but also exhibit a better ability to respond to external stimuli such as pH, 26 ionic strength, and temperature.…”

Section: Introductionmentioning

confidence: 99%

Electrostatic interactions between polyglutamic acid and polylysine yields stable polyion complex micelles for deoxypodophyllotoxin delivery

Wang

Huang

Shen

et al. 2017

IJN

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To achieve enhanced physical stability of poly(ethylene glycol)-poly( d , l -lactide) polymeric micelles (PEG-PDLLA PMs), a mixture of methoxy PEG-PDLLA-polyglutamate (mPEG-PDLLA-PLG) and mPEG-PDLLA-poly( l -lysine) (mPEG-PDLLA-PLL) copolymers was applied to self-assembled stable micelles with polyion-stabilized cores. Prior to micelle preparation, the synthetic copolymers were characterized by 1 H-nuclear magnetic resonance (NMR) and infrared spectroscopy (IR), and their molecular weights were calculated by 1 H-NMR and gel permeation chromatography (GPC). Dialysis was used to prepare PMs with deoxypodophyllotoxin (DPT). Transmission electron microscopy (TEM) images showed that DPT polyion complex micelles (DPT-PCMs) were spherical, with uniform distribution and particle sizes of 36.3±0.8 nm. In addition, compared with nonpeptide-modified DPT-PMs, the stability of DPT-PCMs was significantly improved under various temperatures. In the meantime, the pH sensitivity induced by charged peptides allowed them to have a stronger antitumor effect and a pH-triggered release profile. As a result, the dynamic characteristic of DPT-PCM was retained, and high biocompatibility of DPT-PCM was observed in an in vivo study. These results indicated that the interaction of anionic and cationic charged polyionic segments could be an effective strategy to control drug release and to improve the stability of polymer-based nanocarriers.

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“…9 Even greater pH differences can be found at the cellular level between the extracellular environment (pH 7.4) and intracellular compartments such as the endosomes and lysosomes (pH 4.5-6.5). 21, 22 Lee's group developed a series of pH-responsive vehicles based on poly(ethylene glycol)-b-poly(b-amino ester) using camptothecin and DOX as model drugs, and rapid drug release in weakly tumoral acidic aqueous environments was achieved. 20 To date, a number of pH-responsive polymers have been reported and tested for drug delivery.…”

Section: Introductionmentioning

confidence: 99%

“…Felber et al described some promising examples of pH-sensitive vesicles, polymeric micelles, and nanospheres prepared with polyanionic polymers that exploited acidic microenvironments of cells to trigger the release of drugs from drug delivery systems. 21,22 Lee's group developed a series of pH-responsive vehicles based on poly(ethylene glycol)-b-poly(b-amino ester) using camptothecin and DOX as model drugs, and rapid drug release in weakly tumoral acidic aqueous environments was achieved. 23,24 In general, a well-designed pH-responsive polymer nanocarrier has a long-term stable state in the blood circulation, could respond rapidly to an acidic pH stimulus and consequently release the drugs in the pathological area.…”

Section: Introductionmentioning

confidence: 99%

Precise control of drug release from dually responsive poly(ether urethane) nanoparticles

Wang

et al. 2013

RSC Adv.

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A series of linear poly(ether urethane)s was synthesized based on alternating PEG-diisocyanate of different molecular weight and N-methyldiethanolamine containing ternary amino moieties. The molecular structures of the obtained copolymers were confirmed with nuclear magnetic resonance, Fourier transform infrared spectroscopy and gel permeation chromatography. In aqueous solution, the amphiphilic copolymers could self-assemble into nanoparticles, which showed temperature and pH dual-responsive character. The stimuli-responsive behavior was characterized by light transmission, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. The phase transition temperature (T p ) of the nanoparticles could be modulated by changing the molecular weight of the PEG segments. The encapsulation and release of doxorubicin (DOX) were investigated using the obtained polymeric nanoparticles as carriers. The in vitro experimental results showed that DOX release from the nanoparticles was significantly accelerated when it was conducted at a higher temperature and lower pH value. Importantly, only when the ambient temperature was higher than the corresponding T p , the drug release could be remarkably enhanced by the pH decrease. The system showed a temperaturetriggered pH-dependent drug release. Cell viability and microscopic observation of liver cells (HepG2 cells) treated with the DOX-loaded polymeric nanoparticles demonstrated that the therapeutic activity and the DOX distribution could be precisely controlled by the novel dual-responsive system.

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Preparation of polyion complex micelles from poly(ethylene glycol)-block-polyions

Cited by 31 publications

References 45 publications

Degradable Cationic Shell Cross-Linked Knedel-like Nanoparticles: Synthesis, Degradation, Nucleic Acid Binding, and in Vitro Evaluation

Degradable Cationic Shell Cross-Linked Knedel-like Nanoparticles: Synthesis, Degradation, Nucleic Acid Binding, and in Vitro Evaluation

Electrostatic interactions between polyglutamic acid and polylysine yields stable polyion complex micelles for deoxypodophyllotoxin delivery

Precise control of drug release from dually responsive poly(ether urethane) nanoparticles

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