Premature drug release of polymeric micelles and its effects on tumor targeting

Miller, Tobias; Breyer, Sandra; Colen, Gwenaelle van; Mier, Walter; Haberkorn, Uwe; Geißler, Simon; Voss, Senta; Weigandt, Markus; Goepferich, Achim

doi:10.1016/j.ijpharm.2013.01.059

Cited by 73 publications

(42 citation statements)

References 41 publications

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“…commercially available Doxil Ò and 51 Abraxane Ò . Since the blood circulation maintains a perfect sink con-52 dition, the premature drug release during the journey to the tumour 53 target is inevitable no matter how strong the avidity between the 54 API and the nanocarrier is [4,5]. This significantly contributes to 55 both physical side-effects and psychological harm to the patients.…”

mentioning

confidence: 99%

Tuning the architecture of polymeric conjugate to mediate intracellular delivery of pleiotropic curcumin

Wang

Chen

Zhang

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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confidence: 99%

Tuning the architecture of polymeric conjugate to mediate intracellular delivery of pleiotropic curcumin

Wang

Chen

Zhang

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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“…Delivery systems used in pre-clinical studies exploiting passive targeting include liposomes (Harrington et al, 2000; Wang et al, 2006; Soundararajan et al, 2009; Zheng et al, 2009; Huang et al, 2011; Chen et al, 2012a; Coimbra et al, 2012; Hsu et al, 2012; Mahakian et al, 2014) (Kheirolomoom et al, 2010), micelles (Yokoyama et al, 1999; Le Garrec et al, 2002; Kawano et al, 2006; Reddy et al, 2006; Rijcken et al, 2007; Kim et al, 2008; Hoang et al, 2009; Shiraishi et al, 2009; Blanco et al, 2010; Sumitani et al, 2011; Wang and Gartel, 2011; Zhao et al, 2012; Miller et al, 2013; Zhu et al, 2013), gold nanoparticles (Hainfeld et al, 2006; Von Maltzahn et al, 2009; Puvanakrishnan et al, 2012), iron oxide nanoparticles (Ujiie et al, 2011), silica nanoparticles (Chen et al, 2012b; Di Pasqua et al, 2012), carbon-based nanostructures (Liu et al, 2011; Robinson et al, 2012; Rong et al, 2014), quantum dots (Sun et al, 2014), and hybrid nanomaterials (Balogh et al, 2007; Tinkov et al, 2010; Yang et al, 2012) (Paraskar et al, 2012) (Ohno et al, 2013) (Supplementary Table S1). …”

Section: Tumor Accumulation and Targeting Efficiencymentioning

confidence: 99%

Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

2014

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The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics, tumor accumulation, and biodistribution. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

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“…9 Instability and lack of tumor targeting in vivo are major factors that limit their antitumor efficacy. 10 Effective ways to achieve controlled drug release from micelles include the conjugation of drugs to polymeric materials and the cross-linking of polymers by chemical reactions. 11 Different from passive tumor targeting, which relies on the enhanced permeability and retention (EPR) effect, conjugating specific ligands to drug-loaded particles has become a commonly used method to achieve active tumor targeting.…”

Section: Introductionmentioning

confidence: 99%

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

Zhang¹,

Wu²,

Zhang³

et al. 2017

IJN

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Purpose Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)- block -poly ( d , l -lactide) (mPEG-PDLLA). Methods PTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated. Results The size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was −19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC 0−t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications. Conclusion These results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery.

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Premature drug release of polymeric micelles and its effects on tumor targeting

Cited by 73 publications

References 41 publications

Tuning the architecture of polymeric conjugate to mediate intracellular delivery of pleiotropic curcumin

Tuning the architecture of polymeric conjugate to mediate intracellular delivery of pleiotropic curcumin

Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

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