Hydrazone-Containing Triblock Copolymeric Micelles for pH-Controlled Drug Delivery

Qi, Peilan; Wu, Xiaohe; Liu, Lei; Yu, Huimin; Song, Shiyong

doi:10.3389/fphar.2018.00012

Cited by 38 publications

(20 citation statements)

References 41 publications

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“…32 Hydrazone bond is widely used in pH responsive antitumor drug-delivery systems. 33,34 Therefore, we have synthesized a copolymer modified with hydrazone bond (mPEG-HZ-PLA). It was synthesized via ring-opening polymerization of D,L-lactide with mPEG-HZ-OH as the macroinitiator.…”

Section: Discussionmentioning

confidence: 99%

Targeted pharmacokinetics of polymeric micelles modified with glycyrrhetinic acid and hydrazone bond in H22 tumor-bearing mice

et al. 2019

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Liver cancer is one of the most common malignant tumors. Chemotherapy drugs have been widely used in the anti-hepatoma research. However, low targeting efficiency and serious adverse reaction are their main drawbacks. Liver tumor was proved to have a slightly acidic microenvironment (pH 4.5–5.5) and many glycyrrhetinic-acid-specific binding sites. Therefore, in the present study, the glycyrrhetinic acid- and hydrazone bond-modified micelles were designed. mPEG-HZ-PLA and GA-PEG-PLA copolymer were synthesized to prepare glycyrrhetinic-acid-modified pH-sensitive polymeric micelles (GA-PEG-HZ-PLA). The targeted pharmacokinetics was used to evaluate the effect in hepatoma 22 tumor-bearing mice after the micelles were administered intravenously. The contents of coumarin-6 in blood and tissues were determined through high-performance liquid chromatography using a fluorescence detection (HPLC-FLD) with coumarin-30 as inner standard. The micelles have shown long-circulation effects and two-department models. In the targeting pharmacokinetics, the relative intake efficiency, targeted efficiency, relative targeting efficiency, and concentration ratio of GA-PEG-HZ-PLA in the tumor were 3.24, 4.04, 3.00, and 2.47, respectively. We have demonstrated that GA-PEG-HZ-PLA was more effectively accumulated in the liver and tumor. Thus, the prepared active-targeted and pH-sensitive micelles modified with glycyrrhetinic acid structure and hydrazone bond are promising tools for effective liver cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Targeted pharmacokinetics of polymeric micelles modified with glycyrrhetinic acid and hydrazone bond in H22 tumor-bearing mice

et al. 2019

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“…study, they synthesized polyethylene glycol‐dihyd‐poly lactic acid (PEG‐dihyd‐PLA) micelles containing pH‐sensitive hydrazone bonds, and the release rates of these micelles in physiological (pH 7.4) and acidic environment (pH 4.5) were 38% and 75% in 24 h, respectively. [ 38 ] Lee et al. synthesized doxorubicin‐conjugated poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide (PEO–PPO–PEO) copolymer via a hydrazone bond, and the DOX released out of micelles was 40% and 84% in pH 5 and pH 7.4 after 26 h, respectively.…”

Section: Resultsmentioning

confidence: 99%

HER2‐Targeted, Degradable Core Cross‐Linked Micelles for Specific and Dual pH‐Sensitive DOX Release

Bayram

Ulu

Topuzoğulları

et al. 2021

Macromolecular Bioscience

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Here, a targeted, dual‐pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross‐linking via reversible addition−fragmentation chain‐transfer (RAFT) polymerization with an acid‐sensitive cross‐linker followed by the conjugation of maleimide–doxorubicin to the pyridyl disulfide‐modified micelles. Multifunctional nanocarriers are obtained by coupling HER2‐specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid‐triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX‐conjugated HER2‐specific peptide‐carrying nanocarriers significantly enhance cytotoxicity toward SKBR‐3 cells. More importantly, no selectivity toward MCF‐10A cells is observed compared to HER2(+) SKBR‐3 cells. Formulations cause apoptosis depending on Bax and Caspase‐3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2‐targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH‐sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery.

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“…Through the hydrazone linker, the drug was found to be released in the acidic tumor microenvironment or in the acidic organelles after cellular uptake by endocytosis [70][71][72][73][74][75]. Some more sleuthed polymer-drug conjugates containing hydrazone linkages are HPMA-DOX, PEG-DOX [76,77], PEG-epirubicin [78] and PEG-PTXL [79]. Hydrazone linked acid sensitive PEG-based drug delivery in lysosomes was also studied by Zhu et al, 2012 [74].…”

Section: Polymer-drug Conjugate (A) Dendrimers or Dendriticmentioning

confidence: 99%

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2020

ANN

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Emergence of various nanoscale drug carrier platforms as Drug Delivery Systems (DDS) has revolutionized the field of medicine. Nonetheless, the side-effects due to non-specific distribution of anticancer therapeutics in normal, healthy tissues remains to be a prime pitfall in curing cancers. Therefore, to achieve a better therapeutic efficacy, the use of a target-specific delivery, combined with a stimuli-responsive nanocarrier system, particularly pH-sensitive nanosystems offer an attractive strategy. Targeted drug delivery through pH-sensitive nanosystems offer the potential to enhance the therapeutic index of anticancer agents, either by increasing the drug concentration in tumor cells and/or by decreasing the exposure in normal host tissues. Therefore, nanoscale-based drug delivery through pH-sensitive nanosystems seem to be a boon for treating gynaecological cancers (as well as other cancers) without side-effects or with least harm to normal healthy tissues.

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Hydrazone-Containing Triblock Copolymeric Micelles for pH-Controlled Drug Delivery

Cited by 38 publications

References 41 publications

Targeted pharmacokinetics of polymeric micelles modified with glycyrrhetinic acid and hydrazone bond in H22 tumor-bearing mice

Targeted pharmacokinetics of polymeric micelles modified with glycyrrhetinic acid and hydrazone bond in H22 tumor-bearing mice

HER2‐Targeted, Degradable Core Cross‐Linked Micelles for Specific and Dual pH‐Sensitive DOX Release

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