Antioxidant polymeric prodrug microparticles as a therapeutic system for acute liver failure

Ko, Eunbyul; Jeong, Da‐Hee; Kim, Jihye; Park, Sanga; Khang, Gilson; Lee, Dongwon

doi:10.1016/j.biomaterials.2014.01.048

Cited by 48 publications

(36 citation statements)

References 28 publications

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“…The results showed that compared with non-pretreated groups, PRDSP@DOX NPs in the presence of GSH exhibited higher inhibition efficacy with significantly decreased IC 50 values. While in control groups, the pretreatment of GSH had no impact on the 20 cytotoxicity of HeLa/A549cells cultured with free DOX. The results demonstrated that faster DOX release from PRDSP@DOXNPs could be well triggered by the higher intracellular reduction agent level.…”

Section: In Vitro Cellular Proliferation Assaymentioning

confidence: 81%

“…Cystine was chosen as a raw material with amino groups protected by BOC to introduce the disulfide groups into polymer 20 backbone. To avoid the racemization of L-cystine, BOP was selected as condensation agent instead of DCC or EDC.…”

Section: Results and Discussion Preparation And Characterization Of "mentioning

confidence: 99%

“…4). Similarly, 20 PRDSPNPs were stable at pH 7.4 with little alteration in size, size distribution and morphology, but greatly changed with lowered pH and increased concentration of GSH or H 2 O 2 . …”

Section: Stability Of Prdsp Npsmentioning

confidence: 96%

“…However, the stimulisensitive bonds were usually arranged in the copolymer randomly. We noticed that Cu(I)-catalyzed azide-alkyne cycloaddition 20 (CuAAC) click polymerization was generally used to synthesize functional polymer due to its ordinary manipulation, gentle reaction condition, selectivity and orthogonality with various functional groups. 26,27,28,29,30 CuAAC click polymerization is a very convenient tool to import two or more functions into one 25 system.…”

Section: Introductionmentioning

confidence: 99%

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Novel multi-sensitive pseudo-poly(amino acid) for effective intracellular drug delivery

Zhou

et al. 2015

RSC Adv.

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A novel intracellular pH, glutathione (GSH) and reactive oxygen species (ROS)-responsive nanoparticles were obtained using mPEG 2k -block-redox dual sensitive chain-block-mPEG 2k (PRDSP) which was prepared by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) Click polymerization. The disulfide bond, peroxalate ester and triazole units were regularly and repeatedly arranged in the hydrophobic 10 blocks. The disulfide bond was GSH-sensitive and peroxalate ester structure could be disrupted by acid and hydrogen peroxide. In addition, triazole units are capable of forming pH-responsive hydrogen bonds. Dynamic Light Scattering (DLS) and Transmission electron microscopy (TEM) was used to investigate the pH, GSH and ROS sensitivity of PRDSP nanoparticles (NPs).The results indicated that the average diameter, size distribution and morphology greatly changed upon adding GSH /H 2 O 2 or modulating pH. 15 As the preloaded model anticancer drug, Doxorubicin (DOX) was quickly released from DOX-loaded PRDSP (PRDSP@DOX) NPs by addition of 10 mM Glutathione (GSH), 10 mM H 2 O 2 or under acidic condition rather than under physiological condition. Confocal laser scanning microscopy(CLSM) and flow cytometric analyses revealed that PRDSP@DOX could effectively deliver DOX into the cytoplasm and nucleus of cells. Therefore, PRDSP NPs may be a promising redox heterogeneity-sensitive carrier for 20 efficient and controlled anticancer drug release. 65 entirely destroyed, leading to a slow but incomplete drug release. Drug efficiency is another crucial point. High drug loading content (DLC) and drug loading efficiency (DLE) are commonly

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Section: In Vitro Cellular Proliferation Assaymentioning

confidence: 81%

Section: Results and Discussion Preparation And Characterization Of "mentioning

confidence: 99%

Section: Stability Of Prdsp Npsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Novel multi-sensitive pseudo-poly(amino acid) for effective intracellular drug delivery

Zhou

et al. 2015

RSC Adv.

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“…However, single injection of PVAX nanoparticles into the site of contusion injury in triceps surae muscles and Achilles tendons significantly suppressed the expression of pro-inflammatory cytokines. Therapeutic effects of PVAX nanoparticles can be explained by H 2 O 2 -scavenging and their intrinsic anti-inflammatory activity 27, 30.…”

Section: Resultsmentioning

confidence: 99%

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles

Kim

Kang

et al. 2017

Theranostics

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Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H2O2) are known to be generated during tissue damages such as mechanical injury and therefore H2O2 holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H2O2 and exerts antioxidant and anti-inflammatory activity in H2O2-associated diseases. Based on the notion that PVAX nanoparticles generate CO2 bubbles through H2O2-triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H2O2. In the agarose gel phantom study, PVAX nanoparticles continuously generated CO2 bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H2O2 in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries.

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Multifunctional Supramolecular Filament Hydrogel Boosts Anti‐Inflammatory Efficacy In Vitro and In Vivo

Deng

Lin

Ding

et al. 2022

Adv Funct Materials

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Peptide-drug conjugates (PDCs) are an important class of therapeutic agents that combine one or more active molecules with a short peptide via a biodegradable spacer to generate prodrugs. Here an antioxidant (i.e., 3,5-dihydroxybenzoic acid), a non-steroidal anti-inflammatory drug (i.e., ibuprofen, IPF), and a self-assembled peptide motif (i.e., Gly-Phe-Phe-Tyr-Asp, GFFYD) are integrated to produce a peptide-drug amphiphile, which self-assembles to form hydrogel and further exerts the synergistic effects, and consequently emerges high therapeutic efficacy. In the in vitro study toward lipopolysaccharide-activated RAW264.7 macrophages, the resulting hydrogel significantly reduces the production of cytokines (e.g., IL-1β, IL-6 and tumor necrosis factor-α (i.e., TNF-α)) compared with that of native IPF via the inhibition of nuclear factor-κB (i.e., NF-κB), janus kinase-signal transducer and activator of transcription (i.e., JAK-STAT) signals and NLR family pyrin domain containing 3 (i.e., NLRP3) inflammasome activation. Moreover, a rabbit model of endotoxin induced uveitis evidences the superior therapeutic efficacy of the resulting hydrogel over that of clinically used 0.1 wt% diclofenac sodium eyedrop. Overall, this work offers new insights into the anti-inflammatory mechanism of PDCs hydrogel and presents the therapeutic values in the treatment of ocular disorders, and ultimately fulfils the potential clinical benefits of PDCs.

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Antioxidant polymeric prodrug microparticles as a therapeutic system for acute liver failure

Cited by 48 publications

References 28 publications

Novel multi-sensitive pseudo-poly(amino acid) for effective intracellular drug delivery

Novel multi-sensitive pseudo-poly(amino acid) for effective intracellular drug delivery

Ultrasonographic Imaging and Anti-inflammatory Therapy of Muscle and Tendon Injuries Using Polymer Nanoparticles

Multifunctional Supramolecular Filament Hydrogel Boosts Anti‐Inflammatory Efficacy In Vitro and In Vivo

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