LeGuin, Ursula K(roeber)

Ulbrich, Renate

doi:10.1007/978-3-476-03702-2_207

Cited by 3 publications

(5 citation statements)

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“…The fact that biodegradable diblock conjugates (2P-GEM and 2P-PTX) were more efficient than biodegradable multiblock conjugates reflects most probably the complex solution properties of hydrophilic polymers that contain hydrophobic substituents (drugs) at side chain termini. 45,46 Hydrophobic interactions result in conformation changes of the macromolecule into compact coils as determined previously by light scattering, 45 fluorescence resonance energy transfer (FRET), 46 and quantum yield of singlet oxygen formation 69 techniques. These effects result in decreased solubility in aqueous environment, decrease of rate of enzymatic drug release, or decrease in quantum yield of singlet oxygen formation (when photosensitizers are used).…”

Section: Discussionmentioning

confidence: 61%

“…[17][18][19][20][21][22][23][24]65 It has been shown that the higher the molecular weight of the polymer-drug conjugate, the higher the tumor accumulation and efficacy in an animal model of ovarian carcinoma. 18 However, other factors, such as the conformation of the macromolecule, [45][46][47]65 association of side-chains by hydrophobic interactions (formation of unimolecular micelles), or random association of flexible chains by "point-point" contacts [66][67][68] influence the rate of enzymatic drug release, penetration of the solid tumor, 18,65 and, ultimately, the efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Researchers studied the relationship between the detailed structure of HPMA copolymer-drug conjugates on one hand and their physicochemical and biological properties on the other hand. The impacts of architecture, 25,[40][41][42] structure of spacer between drug and carrier, 3,25,43,44 solution properties (aggregation), 45,46 combination therapy, [47][48][49] targeting stem cells, 50 multivalency, 12,51 and hyperthermia 52 were evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Backbone Degradable N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates with Gemcitabine and Paclitaxel: Impact of Molecular Weight on Activity toward Human Ovarian Carcinoma Xenografts

et al. 2017

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Degradable diblock and multiblock (tetrablock and hexablock) N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-gemcitabine (GEM) and -paclitaxel (PTX) conjugates were synthesized by reversible addition-fragmentation chain-transter (RAFT) copolymerization followed by click reaction for preclinical investigation. The aim was to validate the hypothesis that long-circulating conjugates are needed to generate a sustained concentration gradient between vasculature and a solid tumor and result in significant anticancer effect. To evaluate the impact of molecular weight of the conjugates on treatment efficacy, diblock, tetrablock, and hexablock GEM and PTX conjugates were administered intravenously to nude mice bearing A2780 human ovarian xenografts. For GEM conjugates, triple doses with dosage 5 mg/kg were given on days 0, 7, and 14 (q7dx3), whereas a single dose regime with 20 mg/kg was applied on day 0 for PTX conjugates treatment. The most effective conjugates for each monotherapy were the diblock ones, 2P-GEM and 2P-PTX (Mw ≈ 100 kDa). Increasing the Mw to 200 or 300 kDa resulted in decrease of activity most probably due to changes in the conformation of the macromolecule because of interaction of hydrophobic residues at side chain termini and formation of "unimer micelles". In addition to monotherapy, a sequential combination treatment of diblock PTX conjugate followed by GEM conjugate (2P-PTX/2P-GEM) was also performed, which showed the best tumor growth inhibition due to synergistic effect: complete remission was achieved after the first treatment cycle. However, because of low dose applied, tumor recurrence was observed 2 weeks after cease of treatment. To assess optimal route of administration, intraperitoneal (i.p.) application of 2P-GEM, 2P-PTX, and their combination was examined. The fact that the highest anticancer efficiency was achieved with diblock conjugates that can be synthesized in one scalable step bodes well for the translation into clinics.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Backbone Degradable N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates with Gemcitabine and Paclitaxel: Impact of Molecular Weight on Activity toward Human Ovarian Carcinoma Xenografts

et al. 2017

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“…1,2 For the blood-brain barrier (BBB), where clinical successes have been frustratingly limited for decades, the potential of nanoscale therapies to actively traffic and deliver therapies would attract particular attention. [3][4][5][6] While a wide variety of efforts have been reported, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] progress towards a clinical outcome has been slower than hoped for. Thus, increasingly researchers investigating the potential of nanoscale BBB-related therapies have become convinced that real progress in understanding the detailed mechanisms of interaction between nanoparticles (NPs) and barriers may be a prerequisite for critical advances to occur in the field.…”

mentioning

confidence: 99%

Ultrathin Silicon Membranes for in Situ Optical Analysis of Nanoparticle Translocation across a Human Blood–Brain Barrier Model

et al. 2020

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Here we present a blood-brain barrier (BBB) model that enables high-resolution imaging of nanoparticle (NP) interactions with endothelial cells and the capture of rare NP translocation events. The enabling technology is an ultrathin silicon nitride (SiN) membrane (0.5 μm pore size, 20% porosity, 400 nm thickness) integrated into a dual-chamber platform that facilitates imaging at low working distances (~50 μm). The platform, the μSiM-BBB (microfluidic Silicon Membrane-BBB), features human brain endothelial cells and primary astrocytes grown on opposite sides of the membrane. The human brain endothelial cells form tight junctions on the ultrathin membranes and exhibit a significantly higher resistance to FITC-dextran diffusion than *

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“…used as a chain transfer agent. The polymer, with one carboxylic end group, was purified by ion-exchange chromatography and terminal carboxylic groups were activated as N-hydroxysuccinimide active ester GPC chromatogram of "classical" type (1) and "star-like'' type(2) polymer-drug-antibody conjugates (reaction with N-hydroxysuccinimide was carried out in the presence of dicyclohexylcarbodiimide in DMF). Typical molecular weight (Mw) of the polymer was 15 000.…”

mentioning

confidence: 99%

Polymeric carriers of drugs for site‐specific therapy

Ulbrich¹,

Pechar²,

Strohalm³

et al. 1997

Macromolecular Symposia

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Three types of water-soluble polymeric drug carrier systems facilitating targeted drug delivery and controlled drug release were synthesized. All systems consist of an inert soluble synthetic polymer, drug and homing device (targeting moiety). In the first "classical" system, both drug and targeting moiety are bound to a nondegradable polymer by means of biodegradable oligopeptide side chains statistically distributed along the polymer chain. The second, "star-like'' system contains a targeting moiety (antibody) in the centre and a hydrophilic polymer, bearing drug molecules, in the shell of the system.The third, "biodegradable" carrier system is based on block copolymers of poly(ethy1ene glycol) containing biodegradable oligopeptide sequences both in the main polymer chain and in the spacen between main chain and drug molecules. Strategy and details of the synthesis of all three systems are given.

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LeGuin, Ursula K(roeber)

Cited by 3 publications

References 0 publications

Backbone Degradable N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates with Gemcitabine and Paclitaxel: Impact of Molecular Weight on Activity toward Human Ovarian Carcinoma Xenografts

Backbone Degradable N-(2-Hydroxypropyl)methacrylamide Copolymer Conjugates with Gemcitabine and Paclitaxel: Impact of Molecular Weight on Activity toward Human Ovarian Carcinoma Xenografts

Ultrathin Silicon Membranes for in Situ Optical Analysis of Nanoparticle Translocation across a Human Blood–Brain Barrier Model

Polymeric carriers of drugs for site‐specific therapy

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