Epothilone B-based 3-in-1 polymeric micelle for anticancer drug therapy

Shin, Dae Hwan; Kwon, Glen S.

doi:10.1016/j.ijpharm.2017.01.006

Cited by 19 publications

(16 citation statements)

References 24 publications

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“…Ixabepilone, a semi-synthetic analog of epothilone B, belongs to synthetic chemo drugs with antimitotic properties for treatment of metastatic BC. Epothilones are defined as microtubule inhibitors, highly-effected against PTX-resistant cells [52]. Interestingly, higher effectiveness of Ixabepilone than PTX against resistant cells is caused by the different binding sites of the drug at microtubules.…”

Section: Chemotherapy For Breast Cancermentioning

confidence: 99%

Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer

et al. 2019

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Paclitaxel (PTX), the most widely used anticancer drug, is applied for the treatment of various types of malignant diseases. Mechanisms of PTX action represent several ways in which PTX affects cellular processes resulting in programmed cell death. PTX is frequently used as the first-line treatment drug in breast cancer (BC). Unfortunately, the resistance of BC to PTX treatment is a great obstacle in clinical applications and one of the major causes of death associated with treatment failure. Factors contributing to PTX resistance, such as ABC transporters, microRNAs (miRNAs), or mutations in certain genes, along with side effects of PTX including peripheral neuropathy or hypersensitivity associated with the vehicle used to overcome its poor solubility, are responsible for intensive research concerning the use of PTX in preclinical and clinical studies. Novelties such as albumin-bound PTX (nab-PTX) demonstrate a progressive approach leading to higher efficiency and decreased risk of side effects after drug administration. Moreover, PTX nanoparticles for targeted treatment of BC promise a stable and efficient therapeutic intervention. Here, we summarize current research focused on PTX, its evaluations in preclinical research and application clinical practice as well as the perspective of the drug for future implication in BC therapy.

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Section: Chemotherapy For Breast Cancermentioning

confidence: 99%

Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer

et al. 2019

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Section: ‐Aag‐loaded Nanocarriersmentioning

confidence: 99%

“…In other research designed to enhance the water solubility of epothilone B, rapamycin, and 17‐AAG, Shin and Kwon loaded all three drugs into PEG‐b‐PLA micelles and reported high efficiency of these micelles against A549 cancer cells in vitro and in vivo (Shin & Kwon, ).…”

Section: ‐Aag‐loaded Nanocarriersmentioning

confidence: 99%

“…These drug solubilizers have their own adverse effects including peripheral neurotoxicity and hypersensitivity, and can disturb gastrointestinal function. In addition 17-AAG delivered via DMSO or Cremophor EL has a short half-life, limited ability to reach target cells, induction of drug resistance, poor specificity, and high hepatotoxicity that restrict its clinical use (Shin & Kwon, 2017). In recent years, advances in nanomaterials-based drug delivery carriers have paved the way for overcoming these obstacles (Deldar, Zarghami, Pilehvar-Soltanahmadi, Dadashpour, & Zarghami, 2017;Montazeri et al, 2017).…”

Section: -Aag-loaded Nanocarriersmentioning

confidence: 99%

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Spotlight on 17‐AAG as an Hsp90 inhibitor for molecular targeted cancer treatment

et al. 2019

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Hsp90 is a ubiquitous chaperone with important roles in the organization and maturation of client proteins that are involved in the progression and survival of cancer cells. Multiple oncogenic pathways can be affected by inhibition of Hsp90 function through degradation of its client proteins. That makes Hsp90 a therapeutic target for cancer treatment. 17‐allylamino‐17‐demethoxy‐geldanamycin (17‐AAG) is a potent Hsp90 inhibitor that binds to Hsp90 and inhibits its chaperoning function, which results in the degradation of Hsp90's client proteins. There have been several preclinical studies of 17‐AAG as a single agent or in combination with other anticancer agents for a wide range of human cancers. Data from various phases of clinical trials show that 17‐AAG can be given safely at biologically active dosages with mild toxicity. Even though 17‐AAG has suitable pharmacological potency, its low water solubility and high hepatotoxicity could significantly restrict its clinical use. Nanomaterials‐based drug delivery carriers may overcome these drawbacks. In this paper, we review preclinical and clinical research on 17‐AAG as a single agent and in combination with other anticancer agents. In addition, we highlight the potential of using nanocarriers and nanocombination therapy to improve therapeutic effects of 17‐AAG.

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“…As FEN has low water solubility, only small amounts of it would be present in the water. Hence, FEN would be well encapsulated in polymeric micelles [ 38 , 39 ]. DLS analysis revealed that the average particle size of the FEN-loaded Soluplus ® micelles was 68.3 nm.…”

Section: Resultsmentioning

confidence: 99%

Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Soluplus® Polymeric Micelles Encapsulating Fenbendazole

Jin

Park

et al. 2020

Pharmaceutics

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Fenbendazole (FEN), a broad-spectrum benzimidazole anthelmintic, suppresses cancer cell growth through various mechanisms but has low solubility and achieves low blood concentrations, which leads to low bioavailability. Solubilizing agents are required to prepare poorly soluble drugs for injections; however, these are toxic. To overcome this problem, we designed and fabricated low-toxicity Soluplus® polymeric micelles encapsulating FEN and conducted toxicity assays in vitro and in vivo. FEN-loaded Soluplus® micelles had an average particle size of 68.3 ± 0.6 nm, a zeta potential of −2.3 ± 0.2 mV, a drug loading of 0.8 ± 0.03%, and an encapsulation efficiency of 85.3 ± 2.9%. MTT and clonogenic assays were performed on A549 cells treated with free FEN and FEN-loaded Soluplus® micelles. The in vitro drug release profile showed that the micelles released FEN more gradually than the solution. Pharmacokinetic studies revealed lower total clearance and volume of distribution and higher area under the curve and plasma concentration at time zero of FEN-loaded Soluplus® micelles than of the FEN solution. The in vivo toxicity assay revealed that FEN-loaded Soluplus® micelle induced no severe toxicity. Therefore, we propose that preclinical and clinical safety and efficacy trials on FEN-loaded Soluplus® micelles would be worthwhile.

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Epothilone B-based 3-in-1 polymeric micelle for anticancer drug therapy

Cited by 19 publications

References 24 publications

Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer

Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer

Spotlight on 17‐AAG as an Hsp90 inhibitor for molecular targeted cancer treatment

Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Soluplus® Polymeric Micelles Encapsulating Fenbendazole

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