A comparative study of linear, Y-shaped and linear-dendritic methoxy poly(ethylene glycol)-block-polyamidoamine-block-poly(l-glutamic acid) block copolymers for doxorubicin delivery in vitro and in vivo

Zhang, Yu; Xiao, Chunsheng; Ding, Jianxun; Li, Mingqiang; Chen, Xin; Tang, Zhaohui; Zhuang, Xiuli; Chen, Xuesi

doi:10.1016/j.actbio.2016.04.007

Cited by 21 publications

(13 citation statements)

References 43 publications

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“…We and others have sought to improve PEGylated nanocarrier pharmacokinetics through the use of a brush-like PEG architecture or high molecular weight Y-shaped PEGs, to varying degrees of success. 14,15,28–30 In this study we compared PMPC coronas to these PEG architectures in addition to the linear 5 kDa PEG. We analyzed these polyplex surface materials using a number of techniques that quantify protein adsorption, polyplex stability, in vitro uptake and bioactivity, as well as in vivo pharmacokinetics and tumor gene silencing activity.…”

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confidence: 99%

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

et al. 2017

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Although siRNA-based nanomedicines hold promise for cancer treatment, conventional siRNA–polymer complex (polyplex) nanocarrier systems have poor pharmacokinetics following intravenous delivery, hindering tumor accumulation. Here, we determined the impact of surface chemistry on the in vivo pharmacokinetics and tumor delivery of siRNA polyplexes. A library of diblock polymers was synthesized, all containing the same pH-responsive, endosomolytic polyplex core-forming block but different corona blocks: 5 kDa (benchmark) and 20 kDa linear polyethylene glycol (PEG), 10 kDa and 20 kDa brush-like poly(oligo ethylene glycol), and 10 kDa and 20 kDa zwitterionic phosphorylcholine-based polymers (PMPC). In vitro, it was found that 20 kDa PEG and 20 kDa PMPC had the highest stability in the presence of salt or heparin and were the most effective at blocking protein adsorption. Following intravenous delivery, 20 kDa PEG and PMPC coronas both extended circulation half-lives 5-fold compared to 5 kDa PEG. However, in mouse orthotopic xenograft tumors, zwitterionic PMPC-based polyplexes showed highest in vivo luciferase silencing (>75% knockdown for 10 days with single IV 1 mg/kg dose) and 3-fold higher average tumor cell uptake than 5 kDa PEG polyplexes (20 kDa PEG polyplexes were only 2-fold higher than 5 kDa PEG). These results show that high molecular weight zwitterionic polyplex coronas significantly enhance siRNA polyplex pharmacokinetics without sacrificing polyplex uptake and bioactivity within tumors when compared to traditional PEG architectures.

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confidence: 99%

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

et al. 2017

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“…According to the public reports, in general, DOX-loaded NPs showed a DLC of approximately 10–37% [ 45 , 58 , 59 , 60 , 61 ] and a particle size of approximately 100–270 nm; besides, it was difficult to prepare DOX-loaded NPs with high DLC and small particle size. Compared with these DOX-loaded NPs, α-PGA/DOX NPs presented a significantly enhanced DLC of 66.2% and a small particle size of 110 nm, which could promote its antitumor efficacy.…”

Section: Resultsmentioning

confidence: 99%

Hydrophilic Poly(glutamic acid)-Based Nanodrug Delivery System: Structural Influence and Antitumor Efficacy

Guo

et al. 2022

Polymers

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Poly(amino acids) have advanced characteristics, including unique secondary structure, enzyme degradability, good biocompatibility, and stimuli responsibility, and are suitable as drug delivery nanocarriers for tumor therapy. The isoform structure of poly(amino acids) plays an important role in their antitumor efficacy and should be researched in detail. In this study, two kinds of pH-sensitive isoforms, including α-poly(glutamic acid) (α-PGA) and γ-PGA, were selected and used as nanocarriers to prepare a nanodrug delivery system. According to the preparation results, α-PGA can be used as an ideal drug carrier. Selecting doxorubicin (DOX) as the model drug, an α-PGA/DOX nanoparticle (α-PGA/DOX NPs) with a particle size of 110.4 nm was prepared, and the drug-loading content was 66.2%. α-PGA/DOX NPs presented obvious sustained and pH-dependent release characteristics. The IC50 value of α-PGA/DOX NPs was 1.06 ± 0.77 μg mL−1, decreasing by approximately 8.5 fold in vitro against 4T1 cells after incubation for 48 h. Moreover, α-PGA/DOX NPs enhanced antitumor efficacy in vivo, the tumor inhibition rate was 67.4%, increasing 1.5 fold over DOX injection. α-PGA/DOX NPs also reduced the systemic toxicity and cardiotoxicity of DOX. In sum, α-PGA is a biosafe nanodrug delivery carrier with potential clinical application prospects.

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“…Depending on the biological properties, γ-PGA might be used as food additives, e.g., taste-masking agents, texture modifier, thickeners, stabilizers, moisturizers, and probiotics cryoprotectant [ 12 , 22 , 29 ]. It may be an essential material for maintaining sensitive activities and is used as carriers, fillers, and adhesives in complex matrices, such as for drugs in the medical industry and tissue engineering [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Besides, in agriculture, it can be an ideal stabilizer, metal biosorbent in soil washing, an environment-friendly fertilizer synergist, and plant growth accelerator [ 24 , 38 , 39 , 40 ].…”

Section: The Functional Properties Of γ-Pgamentioning

confidence: 99%

Recent Advances in Microbial Synthesis of Poly-γ-Glutamic Acid: A Review

Hou

Gao

et al. 2022

Foods

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Poly-γ-glutamic acid (γ-PGA) is a natural, safe, non-immunogenic, biodegradable, and environmentally friendly glutamic biopolymer. γ-PGA has been regarded as a promising bio-based materials in the food field, medical field, even in environmental engineering field, and other industrial fields. Microbial synthesis is an economical and effective way to synthesize γ-PGA. Bacillus species are the most widely studied producing strains. γ-PGA biosynthesis involves metabolic pathway of racemization, polymerization, transfer, and catabolism. Although microbial synthesis of γ-PGA has already been used extensively, productivity and yield remain the major constraints for its industrial application. Metabolic regulation is an attempt to solve the above bottleneck problems and meet the demands of commercialization. Therefore, it is important to understand critical factors that influence γ-PGA microbial synthesis in depth. This review focuses on production strains, biosynthetic pathway, and metabolic regulation. Moreover, it systematically summarizes the functional properties, purification procedure, and industrial application of γ-PGA.

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A comparative study of linear, Y-shaped and linear-dendritic methoxy poly(ethylene glycol)-block-polyamidoamine-block-poly(l-glutamic acid) block copolymers for doxorubicin delivery in vitro and in vivo

Cited by 21 publications

References 43 publications

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol

Hydrophilic Poly(glutamic acid)-Based Nanodrug Delivery System: Structural Influence and Antitumor Efficacy

Recent Advances in Microbial Synthesis of Poly-γ-Glutamic Acid: A Review

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