Development of a pH-sensitive polymer using poly(aspartic acid-graft-imidazole)-block-poly(ethylene glycol) for acidic pH targeting systems

Kim, Ji Hoon; Oh, Young-Jin; Lee, Kyung Soo; Yun, Jeong Min; Park, Byung Tae; Oh, Kyung Taek

doi:10.1007/s13233-011-0502-z

Cited by 30 publications

(42 citation statements)

References 40 publications

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“…P(Asp) was prepared as previously reported. 20 The MW of P(Asp) was ~4,000 Da (degree of polymerization =35).…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

“…First, the PLA-PEG diblock copolymer was synthesized by the ring-opening polymerization of L-lactide, initiated by the hydroxyl group of PEG in the presence of Sn[Oct] 2 as a catalyst, as described in previous studies. 20,21 The MW of the prepared PLA-PEG diblock was ~11,000 Da, determined by the 1 H-NMR spectra obtained using a 300 MHz Gemini 2000 NMR instrument (Varian Medical Systems, Palo Alto, CA, USA). For the synthesis of PEG-PLA-PEI copolymer, the terminal hydroxyl group of PLA-PEG (0.18 mmol) was carboxylated with succinic anhydride (0.36 mmol), DMAP (0.18 mmol), TEA (0.18 mmol), and pyridine (0.18 mmol) in DCM (30 mL) at room temperature for 1 day.…”

Section: Synthesis Of Peg-pla-pei Triblock Copolymersmentioning

confidence: 99%

“…20,21 Before loading dox into the complex system, dox⋅HCl was stirred with TEA (2 mol) in DCM overnight to obtain the dox base. PEG-PLA-PEI/P(Asp) (10 mg) and dox (1 mg) were dissolved in 10 mL 50:50 EtOH/DCM solution and transferred into round bottom flasks.…”

Section: Preparation and Characterization Of Dox-loaded Picmentioning

confidence: 99%

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Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

Lim¹,

Youn²,

Lee³

et al. 2016

IJN

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A polyelectrolyte ionomer complex (PIC) composed of cationic and anionic polymers was developed for nanomedical applications. Here, a poly(ethylene glycol)–poly(lactic acid)–poly(ethylene imine) triblock copolymer (PEG–PLA–PEI) and a poly(aspartic acid) (P[Asp]) homopolymer were synthesized. These polyelectrolytes formed stable aggregates through electrostatic interactions between the cationic PEI and the anionic P(Asp) blocks. In particular, the addition of a hydrophobic PLA and a hydrophilic PEG to triblock copolyelectrolytes provided colloidal aggregation stability by forming a tight hydrophobic core and steric hindrance on the surface of PIC, respectively. The PIC showed different particle sizes and zeta potentials depending on the ratio of cationic PEI and anionic P(Asp) blocks (C/A ratio). The doxorubicin (dox)-loaded PIC, prepared with a C/A ratio of 8, demonstrated pH-dependent behavior by the deprotonation/protonation of polyelectrolyte blocks. The drug release and the cytotoxicity of the dox-loaded PIC (C/A ratio: 8) increased under acidic conditions compared with physiological pH, due to the destabilization of the formation of the electrostatic core. In vivo animal imaging revealed that the prepared PIC accumulated at the targeted tumor site for 24 hours. Therefore, the prepared pH-sensitive PIC could have considerable potential as a nanomedicinal platform for anticancer therapy.

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“…P(Asp) was prepared as previously reported. 20 The MW of P(Asp) was ~4,000 Da (degree of polymerization =35).…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

Section: Synthesis Of Peg-pla-pei Triblock Copolymersmentioning

confidence: 99%

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Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

Lim¹,

Youn²,

Lee³

et al. 2016

IJN

Self Cite

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“…While numerous smart nanocarriers have been examined, pH‐sensitive nanocarriers have attracted considerable interest due to their advanced functional properties, such as pH‐dependent release of anticancer agents in unique tumor microenvironments. These environments include tumor extracellular pH (pH ex , ranging from 6.5 to 7.2) as well as endosomal pH (pH en ≤ 6.5) . Moreover, smart polymers with enhanced pH sensitivity show unique functional properties, such as tumor pH‐targeted drug delivery and pH‐triggered drug release.…”

Section: Introductionmentioning

confidence: 99%

“…P(Asp‐ g ‐Im)‐PEG is a polyelectrolyte block copolymer with a pK a of 6.5 and a high buffer capacity for tumor‐targeted drug delivery. Furthermore, micelles prepared using P(Asp‐ g ‐Im)‐PEG showed pH‐dependent physicochemical properties such as critical micelle concentrations, particle sizes, zeta potentials, and morphologies . Based on previous reports, functional NGs were developed using P(Asp‐ g ‐Im)‐PEG.…”

Section: Introductionmentioning

confidence: 99%

Development of pH‐sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid‐graft‐imidazole)‐block‐poly(ethylene glycol)

Sim

Lim

Cho

et al. 2018

J of Applied Polymer Sci

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pH-sensitive nanogels (NGs) based on poly(aspartic acid-graft-imidazole)-poly(ethylene glycol) were developed using linear PEG with different molecular weights (2000 and 4000 Da) as crosslinkers. The pH-sensitive NGs showed reversible size changes during continuously alternating pH changes. The anticancer treatment potential of pH-sensitive NGs was studied using a model drug, irinotecan (IRI). IRI-loaded NGs (ILNs) showed different drug release kinetics in acidic versus neutral pH, in addition to pH-dependent cytotoxicity. Due to its longer crosslinker, ILN 4 (crosslinked with PEG 4000) showed faster IRI release and a greater magnitude of IRI release than ILN 2 (crosslinked with PEG 2000), resulting in greater cytotoxicity against HCT 116 colorectal cancer cells. These pH-sensitive NGs could potentially be used in cancer treatment by mediating the accumulation and release of IRI from ILNs in the acidic tumor environment and by reducing systemic toxicity due to reversible swelling-shrinkage.Recently, poly(amino acid)-based nanogels (NGs) such as poly (L-histidine)-based NGs, 23,24 poly(L-lysine)-based NGs, 25-31 and poly(L-aspartic acid)-based NGs, 32-35 poly(L-glutamic acid)-31,36-38 based NGs have been reported as novel smart nanocarriers with pHsensitive functionality. Chemical crosslinking among pH-sensitive polymers is one method for manipulating the properties of the polymeric micelles. 39,40 Poly(L-histidine)-based NGs showed selective drug release at low pH due to rapid shrinkage at extracellular or cytosolic pHs. Furthermore, endosomal physical disruption was achieved by the considerable volumetric expansion and proton sponge effect that occur at pH en . 41 Other NGs have also shown reversible swelling and drug release after alternating decreases and increases of pH (hereafter referred to as pH cyclization) 25,32 (Figure 1). This reversible swelling and shrinkage of NGs has been studied in the context of treating multidrug resistance tumors. 42 These NGs could release their drug payloads by NG swelling at the low pH of the tumor environment or in the endosomal compartment. After killing the cancer cells and Additional Supporting Information may be found in the online version of this article.

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Synthesis of biomimetic hyperbranched zwitterionic polymers as targeting drug delivery carriers

Wang

Sun

Jiang

et al. 2012

J of Applied Polymer Sci

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Novel biomimetic hyperbranched copolymers that synthesized by polymerization of zwitterionic monomer (CBB) on the surface of a hyperbranched poly(3-ethyl-3-(hydroxymethyl)oxetane) (HBPO) core and used as a drug delivery carrier have been investigated by analysis of protein-adsorption-resistance, cytotoxicity and cell type-specific targeting properties. The as-synthesized biomimetic hyperbranched copolymers showed low toxicity, favorable protein resistant properties and were ultrastable in 100% fetal bovine serum. Folic acid and rodiamin-B were conjugated to the surface of synthesized micelles to endow it with target drug delivery and fluorescence activity, respectively. Intracellular uptake and in vitro cytotoxicity of HBPO-poly(carboxybetaine) micelles were investigated. Doxorubicin was used as a model drug for Hela cells during the experiment. All results show that the biomimetic hyperbranched copolymer is a candidate carrier for target drug delivery.

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Development of a pH-sensitive polymer using poly(aspartic acid-graft-imidazole)-block-poly(ethylene glycol) for acidic pH targeting systems

Cited by 30 publications

References 40 publications

Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

Development of a robust pH-sensitive polyelectrolyte ionomer complex for anticancer nanocarriers

Development of pH‐sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid‐graft‐imidazole)‐block‐poly(ethylene glycol)

Synthesis of biomimetic hyperbranched zwitterionic polymers as targeting drug delivery carriers

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