Hydrolysable core-crosslinked thermosensitive polymeric micelles: Synthesis, characterisation and in vivo studies

Rijcken, Cristianne J.F.; Snel, Cor J.; Schiffelers, Raymond M.; Nostrum, Cornelus F. van; Hennink, Wim E.

doi:10.1016/j.biomaterials.2007.08.047

Cited by 272 publications

(316 citation statements)

References 66 publications

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“…The degradation mechanism of p(HPMAm-lac)-PEG-based hydrogels is due to hydrolysis of the numerous ester bonds present in the polymer networks, as described earlier. 37,41 It was shown that the lactate side chains of p(HPMAm-lac) with a free terminal OH group are hydrolyzed in approximately 1 week. The terminal lactate moiety in the HPMAm-dilactate is degraded faster than the one in the HPMAm-monolactate, because by a nucleophilic attack of the hydroxy terminus, the ester bond that is located two lactate units further on in the side chain is hydrolyzed in a so-called backbiting mechanism.…”

Section: Resultsmentioning

confidence: 99%

Photopolymerized Thermosensitive Poly(HPMAlactate)-PEG-Based Hydrogels: Effect of Network Design on Mechanical Properties, Degradation, and Release Behavior

et al. 2010

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Photopolymerized thermosensitive A-B-A triblock copolymer hydrogels composed of poly(N-(2-hydroxypropyl)-methacrylamide lactate) A-blocks, partly derivatized with methacrylate groups to different extents (10, 20, and 30%) and hydrophilic poly(ethylene glycol) B-blocks of different molecular weights (4, 10, and 20 kDa) were synthesized. The aim of the present study was to correlate the polymer architecture with the hydrogel properties, particularly rheological, swelling, degradation properties and release behavior. It was found that an increasing methacrylation extent and a decreasing PEG molecular weight resulted in increasing gel strength and cross-link density, which tailored the degradation profiles from 25 to more than 300 days. Polymers having small PEG blocks showed a remarkable phase separation into polymer-and water-rich domains, as demonstrated by confocal microscopy. Depending on the hydrophobic domain density, the loaded protein resides in the hydrophilic pores or is partitioned into hydrophilic and hydrophobic domains, and its release from these compartments is tailored by the extent of methacrylation and by PEG length, respectively. As the mechanical properties, degradation, and release profiles can be fully controlled by polymer design and concentration, these hydrogels are suitable for controlled protein release.

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Section: Resultsmentioning

confidence: 99%

Photopolymerized Thermosensitive Poly(HPMAlactate)-PEG-Based Hydrogels: Effect of Network Design on Mechanical Properties, Degradation, and Release Behavior

et al. 2010

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“…This is due to micelle stability is a function of both thermodynamic and kinetic parameters. When the concentration of polymers below the critical micelle concentration (CMC), premature micelle should disassemble rapidly and release its payloads quickly (12). To overcome this drawback, two strategies are often used to develop these micelles are able to stably retain the drug for a prolonged time in the circulation before micelles arriving their target for releasing their payloads.…”

Section: Introductionmentioning

confidence: 99%

Stability Influences the Biodistribution, Toxicity, and Anti-tumor Activity of Doxorubicin Encapsulated in PEG-PE Micelles in Mice

et al. 2012

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Purpose To investigate the influences of stability of doxorubicin (DOX) retained in PEG-PE/HSPC micelles on its biodistribution, toxicity and anti-tumor activity in mice. Methods We incorporated HSPC into PEG-PE micelles at various molar ratios by a self-assembly procedure. Micelles were characterized by dynamic light scattering, transmission electron microscope, atomic force microscopy. Agarose gel electrophoresis assay was used to detect stable retention of DOX in micellar preparations. Biodistribution, toxicity and antitumor activity of doxorubicin encapsulated in PEG-PE/HSPC micelles in mice were investigated. Results HSPC incorporation not only changed the size and shape of PEG-PE micelles, but also decreased the ability of DOX stable retained in PEG-PE micelles, resulting in a great discrepancy in biodistribution, toxicity and anti-tumor activity among micellar DOX preparations. DOX encapsulated in PEG-PE micelles (M 1 -DOX), with narrower size distribution and greater stability, demonstrated better cytotoxicity in vitro and low systemic toxicity with superior anti-tumor metastasis activity in vivo. Conclusions Encapsulation of DOX into PEG-PE micelles showed the best therapeutic activity and lowest systemic toxicity compared to other HSPC-incorporated PEG-PE micellar preparations. Stable retention of drugs within micelles is important and is determined by compatibility between drugs and polymer blocks.

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“…61 However, low stability of micelles in circulation remains the critical challenge. 62 As shown in this study, PTX-CMs significantly prolonged systemic circulation time compared to PTX-Ms and Taxol ( Figure 3, Table 3). Pharmacokinetic and in vitro release results demonstrated that NaC improved the stability of micelles and achieved sustained release of PTX in vitro and in vivo.…”

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confidence: 72%

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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Hydrolysable core-crosslinked thermosensitive polymeric micelles: Synthesis, characterisation and in vivo studies

Cited by 272 publications

References 66 publications

Photopolymerized Thermosensitive Poly(HPMAlactate)-PEG-Based Hydrogels: Effect of Network Design on Mechanical Properties, Degradation, and Release Behavior

Photopolymerized Thermosensitive Poly(HPMAlactate)-PEG-Based Hydrogels: Effect of Network Design on Mechanical Properties, Degradation, and Release Behavior

Stability Influences the Biodistribution, Toxicity, and Anti-tumor Activity of Doxorubicin Encapsulated in PEG-PE Micelles in Mice

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

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