Reduction-sensitive mixed micelles assembled from amphiphilic prodrugs for self-codelivery of DOX and DTX with synergistic cancer therapy

Wu, Jilian; Zhang, Huiyuan; Hu, Xu; Liu, Ruiling; Jiang, Wei; Li, Zhonghao; Luan, Yuxia

doi:10.1016/j.colsurfb.2017.11.011

Cited by 22 publications

(6 citation statements)

References 31 publications

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“…13 Micelles are considered to be efficient drug carriers owing to their small size and ability to solubilize hydrophobic drugs. 14,15 In addition, micelles have shown great potential as carriers of anticancer therapeutics. [15][16][17] Recently, an aqueous-soluble form of natural vitamin E, known as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), has gained attention as a promising pharmaceutical excipient for developing amphiphilic micelles (alone or mixed with other biomaterials) and are capable of encapsulating hydrophobic drugs.…”

Section: Introductionmentioning

confidence: 99%

“…14,15 In addition, micelles have shown great potential as carriers of anticancer therapeutics. [15][16][17] Recently, an aqueous-soluble form of natural vitamin E, known as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), has gained attention as a promising pharmaceutical excipient for developing amphiphilic micelles (alone or mixed with other biomaterials) and are capable of encapsulating hydrophobic drugs. 18,19 Nasal drug administration has attracted considerable attention in the field of drug delivery due to the distinct advantages that it can offer.…”

Section: Introductionmentioning

confidence: 99%

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In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance

Ahmed¹,

Badr-Eldin²

2018

IJN

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BackgroundRaloxifene hydrochloride (RLX) is approved by the US Food and Drug Administration for the treatment and prevention of osteoporosis, in addition to reducing the risk of breast cancer in postmenopausal women. RLX has the disadvantages of low aqueous solubility, extensive presystemic intestinal glucuronidation, and first-pass metabolism, resulting in a limited bio-availability of only 2%. The aim of this work was to enhance the bioavailability of RLX via the formulation of an in situ nasal matrix (misemgel) comprising micelles made of vitamin E and D-α-tocopheryl polyethylene glycol 1000 succinate and nanosized self-emulsifying systems (NSEMS).Materials and methodsOptimization of the RLX-loaded NSEMS was performed using a mixture design. The formulations were characterized by particle size and then incorporated into an in situ nasal gel. Transmission electron microscopy, bovine nasal mucosa ex vivo permeation, and visualization using a fluorescence laser microscope were carried out on the RLX in situ misemgel comparing with raw RLX in situ gel. In addition, the in vivo performance was studied in rats.ResultsThe results revealed improved permeation parameters for RLX misemgel compared with control gel, with an enhancement factor of 2.4. In vivo studies revealed a 4.79- and 13.42-fold increased bioavailability for RLX in situ misemgel compared with control RLX in situ gel and commercially available tablets, respectively. The obtained results highlighted the efficacy of combining two different formulations to enhance drug delivery and the benefits of utilizing different possible paths for drug absorption.ConclusionThe developed in situ misemgel matrix could be considered as a promising multifunctional platform for nasal delivery which works based on a dual-absorption mechanism.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance

Ahmed¹,

Badr-Eldin²

2018

IJN

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“…Docetaxel, a microtubule stabilizer similar to paclitaxel, has also been subject to similar attempts. Delivery of docetaxel and doxorubicin was demonstrated using PEG–PCL micelles [127]. PEG–PCL diblock copolymers conjugated to wither docetaxel or doxorubicin via disulfide bonds were mixed in a 1:1 ratio and self-assembled in water to yield micelles.…”

Section: Delivering Combination Therapiesmentioning

confidence: 99%

Delivering Combination Chemotherapies and Targeting Oncogenic Pathways via Polymeric Drug Delivery Systems

Nair

2019

Polymers

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The side-effects associated with chemotherapy necessitates better delivery of chemotherapeutics to the tumor. Nanoparticles can load higher amounts of drug and improve delivery to tumors, increasing the efficacy of treatment. Polymeric nanoparticles, in particular, have been used extensively for chemotherapeutic delivery. This review describes the efforts made to deliver combination chemotherapies and inhibit oncogenic pathways using polymeric drug delivery systems. Combinations of chemotherapeutics with other drugs or small interfering RNA (siRNA) combinations have been summarized. Special attention is given to the delivery of drug combinations that involve either paclitaxel or doxorubicin, two popular chemotherapeutics in clinic. Attempts to inhibit specific pathways for oncotherapy have also been described. These include inhibition of oncogenic pathways (including those involving HER2, EGFR, MAPK, PI3K/Akt, STAT3, and HIF-1α), augmentation of apoptosis by inhibiting anti-apoptosis proteins (Bcl-2, Bcl-xL, and survivin), and targeting dysregulated pathways such as Wnt/β-catenin and Hedgehog.

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“…Therefore, the development of nanocarriers in response to GSH is considered to be a potential method for targeted delivery of anticancer drugs. The most common structure used in reduction responsive polymeric micelles is the disulfide bond (-S-S-) [ 18 , 19 , 20 , 21 ], which can be kept stable in plasma and broken in reduction conditions. The extracellular oxidation environment and intracellular reduction environment make it an important tool for the design of tumor microenvironment responsive polymeric micelles [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release

Yang

Shan

et al. 2021

Pharmaceutics

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At present, the drug is still difficult to release completely and quickly only with single stimulation. In order to promote the rapid release of polymeric micelles at tumor site, pH/reduction sensitive polymers (PCT) containing disulfide bonds and orthoester groups were synthesized. The PCT polymers can self-assemble in water and entrap doxorubicin to form drug-loaded micelles (DOX/PCT). In an in vitro drug release experiment, the cumulative release of DOX/PCT micelles in the simulated tumor microenvironment (pH 5.0 with GSH) reached (89.7 ± 11.7)% at 72 h, while it was only (16.7 ± 6.1)% in the normal physiological environment (pH 7.4 without GSH). In addition, pH sensitive DOX loaded micellar system (DOX/PAT) was prepared as a control. Furthermore, compared with DOX/PAT micelles, DOX/PCT micelles showed the stronger cytotoxicity against tumor cells to achieve an effective antitumor effect. After being internalized by clathrin/caveolin-mediated endocytosis and macropinocytosis, DOX/PCT micelles were depolymerized in intercellular acidic and a reductive environment to release DOX rapidly to kill tumor cells. Additionally, DOX/PCT micelles had a better inhibitory effect on tumor growth than DOX/PAT micelles in in vivo antitumor activity studies. Therefore, pH/reduction dual sensitive PCT polymers have great potential to be used as repaid release nanocarriers for intercellular delivery of antitumor drugs.

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Reduction-sensitive mixed micelles assembled from amphiphilic prodrugs for self-codelivery of DOX and DTX with synergistic cancer therapy

Cited by 22 publications

References 31 publications

In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance

In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance

Delivering Combination Chemotherapies and Targeting Oncogenic Pathways via Polymeric Drug Delivery Systems

Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release

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