Intelligent polymeric micelles from functional poly(ethylene glycol)-poly(amino acid) block copolymers

Bae, Younsoo; Kataoka, Kazunori

doi:10.1016/j.addr.2009.04.016

Cited by 602 publications

(398 citation statements)

References 71 publications

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“…PEG is usually selected as the shell-forming segment because of its physicochemical characteristics, including high water solubility through steric stabilisation, significant chain mobility, lower toxicity and a stealth effect on the polymeric micelles preventing the adsorption of proteins [122]. Polymeric micelles have demonstrated good stability at low concentrations, adequate size for systemic drug delivery, useful out-shell emplacement for active targeting and feasibility for multiple drug incorporation towards combination therapy applications [123]. Kataoka and co-workers are pioneers in this area with several block co-polypeptide micelles in clinical trials as anticancer agents [124] (Table 1), and many similar analogues in preclinical evaluation, e.g., NC-6301 (analogue of NK911 with docetaxel) and NC-4016 [analogue of NC-6004 with oxaliplatin (DACH-platinate)] [31,125].…”

Section: Drug Deliverymentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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Abstract:Polypeptides are envisaged to achieve a major impact on a number of different relevant areas such as biomedicine and biotechnology. Acquired knowledge and the increasing interest on amino acids, peptides and proteins is establishing a large panel of these biopolymers whose physical, chemical and biological properties are ruled by their controlled sequences and composition. Polymer therapeutics has helped to establish these polypeptide-based constructs as polymeric nanomedicines for different applications, such as disease treatment and diagnostics. Herein, we provide an overview of the advantages of these systems and the main methodologies for their synthesis, highlighting the different polypeptide architectures and the current research towards clinical applications.

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Section: Drug Deliverymentioning

confidence: 99%

Peptide-Based Polymer Therapeutics

2014

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“…Although many types of amphiphilic block copolymers can form micelles, extensive studies have shown that the hybrid polypeptides of poly(ethylene glycol) (PEG)-b-poly(amino acids) copolymers are possibly the most suitable components for designing PMs, 3,4 due to their excellent biocompatibility and various functional groups, such as carboxyl and amino, which can be easily tailored to allow drug incorporation or the production of versatile copolymers.…”

Section: Introductionmentioning

confidence: 99%

Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers

Gu¹,

Xu²,

Sui³

et al. 2012

IJN

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Abstract:In this work, racemic hybrid polypeptides poly(ethylene glycol) (PEG)-bpoly(racemic-leucine) (PRL) copolymers with different leucine residues have been synthesized and characterized. Using docetaxel as a model molecule, the high drug-loaded spherical micelles based on PEG-PRL were prepared successfully using dialysis, with a tunable particle size from 170 nm to 250 nm obtained by changing the length of the hydrophobic blocks. Facilitated drugloading behavior (higher drug-loading ability and easier drug-loading process) of PEG-PRL compared with their corresponding levo forms (PEG-b-poly[levo leucine]) was observed and clarified for the first time. With this facilitation, the highest drug-loading content and efficiency of PEG-PRL micelles can achieve 11.2% ± 0.4% and 67.2% ± 2.4%, respectively. All drugloaded PEG-PRL micelles exhibit a similar release behavior with a sustained release up to 72 hours. The PEG-PRL was shown to be nontoxic against MCF-7 and human umbilical vein endothelial cells up to a concentration of 100 μg/mL, displaying a good biocompatibility. Also, the docetaxel-loaded PEG-PRL micelles were more toxic than the free drug against MCF-7 human breast cancer cells -both dose and time dependent. Therefore, these high docetaxel-loaded micelles based on racemic hybrid polypeptides appear to be a novel promising nanomedicine for anticancer therapy.

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“…Among these formulations, polymer micelles offer a versatile platform that can be prepared through self-assembling of block copolymers in aqueous solutions. 20 Self-assembled polymer micelles possess a core compartment enveloped by a hydrophilic shell. The core-shell structure protects drug payloads from precipitation, protein adsorption, and enzymatic degradation in the body.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity

Scott

Rohr

Bae

2011

IJN

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Mithramycin (MTM), a natural product of soil bacteria from the Streptomyces genus, displays potent anticancer activity but has been limited clinically by severe side effects and toxicities. Engineering of the MTM biosynthetic pathway has produced the 3-side-chain-modified analogs MTM SK (SK) and MTM SDK (SDK), which have exhibited increased anticancer activity and improved therapeutic index. However, these analogs still suffer from low bioavailability, short plasma retention time, and low tumor accumulation. In an effort to aid with these shortcomings, two nanoparticulate formulations, poly(ethylene glycol)-poly(aspartate hydrazide) self-assembled and cross-linked micelles, were investigated with regard to the ability to load and pH dependently release the drugs. Micelles were successfully formed with both nanoparticulate formulations of each drug analog, with an average size of 8.36 ± 3.21 and 12.19 ± 2.77 nm for the SK and SDK micelles and 29.56 ± 4.67 nm and 30.48 ± 7.00 nm for the SK and SDK cross-linked micelles respectively. All of the drug-loaded formulations showed a pH-dependent release of the drugs, which was accelerated as pH decreased from 7.4 to 5.0. The micelles retained biological activity of SK and SDK entrapped in the micelles, suppressing human A549 lung cancer cells effectively.

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Intelligent polymeric micelles from functional poly(ethylene glycol)-poly(amino acid) block copolymers

Cited by 602 publications

References 71 publications

Peptide-Based Polymer Therapeutics

Peptide-Based Polymer Therapeutics

Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers

Nanoparticulate formulations of mithramycin analogs for enhanced cytotoxicity

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