Novel thermo-sensitive core–shell nanoparticles for targeted paclitaxel delivery

Li, Yuanpei; Pan, Shaowei; Zhang, Wei; Du, Zhuo

doi:10.1088/0957-4484/20/6/065104

Cited by 50 publications

(35 citation statements)

References 41 publications

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“…To date several acid-responsive and thermo-sensitive polymers of paclitaxel have been described that improve the water-solubility and increase the tumor-specificity of the widely used anti-neoplastic drug, paclitaxel [30,31]. However, to the best of our knowledge, no examples of polymer paclitaxel conjugates have been reported that incorporate both acid-sensitive as well as heat-responsive features that are designed to simultaneously amplify the release and targeting of paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis

Moktan

Ryppa²,

Kratz³

et al. 2010

Invest New Drugs

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Poor aqueous solubility limits the therapeutic index of paclitaxel as an anti-cancer drug. Synthesis of soluble prodrugs of paclitaxel, or conjugation of the drug to macromolecular carriers have been reported to increase its water-solubility. Macromolecular drug carriers have an added advantage of targeting the drug to the tumor site due to the abnormal tumor blood and lymphatic vasculature. This study describes a thermally responsive macromolecular carrier, elastin-like polypeptide (ELP) for the delivery of paclitaxel. Paclitaxel was bound to ELP by conjugation with the 6-maleimidocaproyl hydrazone derivative of paclitaxel, an acid-sensitive paclitaxel prodrug, for the potential treatment of breast cancer. Focused hyperthermia above a specific transition temperature at the site of a tumor causes ELP to aggregate and accumulate, thereby increasing the local concentration of the drug cargo. The paclitaxel prodrug described here bears an acid-sensitive linker that is cleavable at the lysosomal/endosomal pH, which allows a controlled intracellular release of the drug. The ELP-delivered paclitaxel in the presence of hyperthermia inhibits MCF-7 cell proliferation by stabilizing the microtubule structures, arresting the cells at the G2/M stage, and inducing apoptosis in a manner similar to conventional paclitaxel. It also inhibits proliferation of a paclitaxel resistant MCF-7 cell line. These data provide an in vitro proof of concept for the use of ELP as a delivery vehicle of paclitaxel.

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Section: Discussionmentioning

confidence: 99%

A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis

Moktan

Ryppa²,

Kratz³

et al. 2010

Invest New Drugs

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“…50,51) A solution of BSA (45 mg·mL −1 ) in 0.15 M PBS pH 7.4, which was similar to the concentration found in plasma, was prepared and mixed with CnCA nanoparticles.…”

Section: Preparation Of Ptx-loaded Calixarene Nanoparticlesmentioning

confidence: 99%

Preparation and Characterization of Amphiphilic Calixarene Nanoparticles as Delivery Carriers for Paclitaxel

Zhao

Wang

Han

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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Two types of amphoteric calix[n]arene carboxylic acid (CnCA) derivative, i.e., calix[6]arene hexa-carboxylic acid (C 6 HCA) and calix[8]arene octo-carboxylic acid (C 8 OCA), were synthesized by introducing acetoxyls into the hydroxyls of calix[n]arene (n 6, 8). C 6 HCA and C 8 OCA nanoparticles (NPs) were prepared successfully using the dialysis method. CnCA NPs had regular spherical shapes with an average diameter of 180-220 nm and possessed negative charges of greater than 30 mV. C 6 HCA and C 8 OCA NPs were stable in 4.5% bovine serum albumin solutions and buffers (pH 5-9), with a low critical aggregation concentration value of 5.7 mg·L 1 and 4.0 mg·L 1 , respectively. C 6 HCA and C 8 OCA NPs exhibited good paclitaxel (PTX) loading capacity, with drug loading contents of 7.5% and 8.3%, respectively. The overall in vitro release behavior of PTX from the CnCA NPs was sustained, and C 8 OCA NPs had a slower release rate compared with C 6 HCA NPs. These favorable properties of CnCA NPs make them promising nanocarriers for tumortargeted drug delivery.Key words calix[n]arene carboxylic acid; nanoparticle; paclitaxel; tumor therapy Paclitaxel (PTX) is a well-known anticancer drug that is used primarily to treat lung, breast and ovarian cancers. Similar to most anticancer drugs, its poor solubility in water limits the clinical applications of PTX. Taxol, a widely used clinical formulation of paclitaxel, requires the use of Cremphor-EL as a solubilizer, which has been known to cause serious problems, including hypersensitivity reactions, neurotoxicity, and nephrotoxicity.1,2) Moreover, the lack of selectivity of PTX results in significant toxicity to noncancerous cells and severely impacts patients' quality of life. Therefore, there is a dire need for the development of a novel formulation that improves the solubility of PTX and decreases its side effects.Among various alternatives, nano-sized drug delivery system (nano-DDS) is one of the best choices. Nano-DDS not only greatly enhances the solubility of PTX without side effects, but it also promotes intra-tumoral drug accumulation through the enhanced permeability and retention (EPR) effect.3,4) Many nano-DDSs of PTX have been reported, and some of them have been marketed. Abraxane, a nanosuspension of paclitaxel encapsulated in human albumin was approved by the Food and Drug Administration (FDA) in 2005 for the treatment of metastatic breast cancer.5) A liposomebased PTX formulation, Lipusu, has been applied for the treatment of ovarian cancer in China.6) In addition to these approved drugs, a number of PTX nano-DDSs, such as polymeric nanoparticles (NPs), 7-9) inorganic NPs, 10) nano-emulsions, 11) carbon nanotubes, 12) and nanogels, 13) have been reported in preclinical studies. Although these novel PTX nano-DDSs exhibit varying levels of success, methods for improving the safety, stability and specificity of nano-DDS still warrant further research.Calixarenes have been used as an important class of macrocyclic host molecules in supramolecular chemistry.14) Becaus...

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“…With the invention of large-scale hyperthermia instruments and the wide use of hyperthermia, thermal targeting has become much easier to implement and more precise to control (Johannsen et al, 2006;Paciotti et al, 2006;Sayed et al, 2006;Visaria et al, 2006;Yang et al, 2007Yang et al, , 2009Liu et al, 2008;Shen et al, 2008;Li et al, 2009d). Thermal targeting has the following obvious advantages: (1) Compared to other techniques such as active targeting, it can be applied on a wide spectrum of cancer types as it relies on local heating to confine the release of drugs.…”

Section: Physical and Chemical Targeting Tcm Preparationmentioning

confidence: 99%

Application of traditional Chinese medicine preparation in targeting drug delivery system

Xing

Dong

et al. 2014

Drug Delivery

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(2015) Application of traditional Chinese medicine preparation in targeting drug delivery system, Drug Delivery, 22:3, 258-265, DOI: 10.3109/10717544.2014 AbstractTargeting drug system (TDS) or targeted drug delivery system (TDDS) is a new kind of drug delivery system which could make drug to be directly concentrated on the target site with high curative effects and low side-effects. As the quintessence of Chinese culture, traditional Chinese medicine (TCM) has a large advantage in many disease clinical treatments, especially in cancer, hypertension and many other intractable diseases owing to their low toxicity and side-effects relative to western medicine. This article reviews literatures on development of TCM-targeted preparations which were published in the past 10 years. TDS including active-targeting, passive-targeting and physical-chemical-targeting preparations were introduced through domestic and overseas literatures to reveal the unique advantages of TCM-targeting preparations in drug delivery system. In this article, we have reviewed some kinds of TCM-targeting preparations and indicated that great attention should be paid to the research on the TCM-targeting preparations.

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Novel thermo-sensitive core–shell nanoparticles for targeted paclitaxel delivery

Cited by 50 publications

References 41 publications

A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis

A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis

Preparation and Characterization of Amphiphilic Calixarene Nanoparticles as Delivery Carriers for Paclitaxel

Application of traditional Chinese medicine preparation in targeting drug delivery system

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