Polymer Therapeutics: Concepts and Applications

Haag, Rainer; Kratz, Felix

doi:10.1002/anie.200502113

Cited by 1,073 publications

(823 citation statements)

References 149 publications

(124 reference statements)

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“…Biocompatible polymer conjugates are effective drug delivery systems for diagnostics and therapeutics [1][2][3][4]. Water-soluble biomedical polymers have a prolonged blood circulation time and the conjugation of diagnostics and therapeutics to the polymers significantly modify their pharmacokinetics and pharmacodynamics.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Visualization of in Vivo Drug Delivery of Poly(l-glutamic acid) Using Contrast-Enhanced MRI

Jeong

et al. 2006

Mol. Pharmaceutics

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Biomedical imaging is valuable for non-invasive investigation of in vivo drug delivery with polymer conjugates. It can provide real-time information on pharmacokinetics, biodistribution and drug delivery efficiency of the conjugates. Non-invasive visualization of in vivo drug delivery of polymer conjugates with contrast enhanced magnetic resonance imaging (MRI) was studied with paramagnetically labeled poly(L-glutamic acid) in an animal tumor model. Poly(L-glutamic acid) is a biocompatible and biodegradable drug carrier for diagnostics and therapeutics. Poly(L-glutamic acid)-1,6-hexanediamine-(Gd-DO3A) conjugates with molecular weights of 87, 50 and 28 KDa and narrow molecular weight distributions were prepared and studied in mice bearing MDA-MB-231 human breast cancer xenografts. Contrast enhanced MRI resulted in real-time and three-dimensional visualization of blood circulation, pharmacokinetics, biodistribution and tumor accumulation of the conjugates, and the size effect on these pharmaceutics properties. The conjugate of 28 KDa rapidly cleared from the circulation and had a relatively lower tumor accumulation. The conjugates with higher molecular weights exhibited a more prolonged blood circulation and higher tumor accumulation. The difference between the conjugates of 87 and 50 KDa was not significant. Contrast enhanced MRI is effective for non-invasive real-time visualization of in vivo drug delivery of paramagnetically labeled polymer conjugates.

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Section: Introductionmentioning

confidence: 99%

Noninvasive Visualization of in Vivo Drug Delivery of Poly(l-glutamic acid) Using Contrast-Enhanced MRI

Jeong

et al. 2006

Mol. Pharmaceutics

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“…Polymeric delivery systems can also enhance the aqueous solubility and modify the pharmacokinetics and biodistribution of lipophilic drugs [5][6][7][8][9][10][11][12] . However, not all polymeric nanocarriers work efficiently.…”

mentioning

confidence: 99%

Poly-cyclodextrin and poly-paclitaxel nano-assembly for anticancer therapy

et al. 2014

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Effective anticancer therapy can be achieved by designing a targeted drug-delivery system with high stability during circulation and efficient uptake by the target tumour cancer cells. We report here a novel nano-assembled drug-delivery system, formed by multivalent host-guest interactions between a polymer-cyclodextrin conjugate and a polymer-paclitaxel conjugate. The multivalent inclusion complexes confer high stability to the nano-assembly, which efficiently delivers paclitaxel into the targeted cancer cells via both passive and active targeting mechanisms. The ester linkages between paclitaxel and the polymer backbone permit efficient release of paclitaxel within the cell by degradation. This novel targeted nano-assembly exhibits significant antitumour activity in a mouse tumour model. The strategy established in this study also provides knowledge for the development of advanced anticancer drug delivery.

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“…S ynthetic nanoparticles (NPs) that are capable of recognizing and capturing venomous biomacromolecules and neutralizing their toxicity in vivo are of significant interest as a new class of antidote (1)(2)(3)(4). Compared to small molecular antidotes, they cover a much wider area of the surface of target macromolecules through multipoint interactions, which enables efficient neutralization of the targets' toxicity.…”

mentioning

confidence: 99%

The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo

Hoshino

Koide

Furuya

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

178

213

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Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a "corona" of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes.

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Polymer Therapeutics: Concepts and Applications

Cited by 1,073 publications

References 149 publications

Noninvasive Visualization of in Vivo Drug Delivery of Poly(l-glutamic acid) Using Contrast-Enhanced MRI

Noninvasive Visualization of in Vivo Drug Delivery of Poly(l-glutamic acid) Using Contrast-Enhanced MRI

Poly-cyclodextrin and poly-paclitaxel nano-assembly for anticancer therapy

The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo

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