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Record W2315034049 · doi:10.1021/bc200284b

Synthetic Modification of Carboxymethylcellulose and Use Thereof to Prepare a Nanoparticle Forming Conjugate of Docetaxel for Enhanced Cytotoxicity against Cancer Cells

2011· article· en· W2315034049 on OpenAlexaff
Mark J. Ernsting, Wei-Lun Tang, Noah MacCallum, Shyh‐Dar Li

Bibliographic record

VenueBioconjugate Chemistry · 2011
Typearticle
Languageen
FieldMaterials Science
TopicNanoparticle-Based Drug Delivery
Canadian institutionsOntario Institute for Cancer Research
Fundersnot available
KeywordsChemistryConjugateNanoparticleDocetaxelEthylene glycolPEGylationPEG ratioCytotoxicitySolubilityDrug deliveryNanocarriersCombinatorial chemistryNuclear chemistryNanotechnologyOrganic chemistryIn vitroPolyethylene glycolBiochemistryCancerMaterials science

Abstract

fetched live from OpenAlex

A nanoparticle formulation of docetaxel (DTX) was designed to address the strengths and limitations of current taxane delivery systems: PEGylation, high drug conjugation efficiency (>30 wt %), a slow-release mechanism, and a well-defined and stable nanoparticle identity were identified as critical design parameters. The polymer conjugate was synthesized with carboxymethylcellulose (CMC), an established pharmaceutical excipient characterized by a high density of carboxylate groups permitting increased conjugation of a drug. CMC was chemically modified through acetylation to eliminate its gelling properties and to improve solvent solubility, enabling high yield and reproducible conjugation of DTX and poly(ethylene glycol) (PEG). The optimal conjugate formulation (Cellax) contained 37.1 ± 1.5 wt % DTX and 4.7 ± 0.8 wt % PEG, exhibited a low critical aggregation concentration of 0.6 μg/mL, and formed 118-134 nm spherical nanoparticles stable against dilution. Conjugate compositions with a DTX degree of substitution (DS) outside the 12.3-20.8 mol % range failed to form discrete nanoparticles, emphasizing the importance of hydrophobic and hydrophilic balance in molecular design. Cellax nanoparticles released DTX in serum with near zero order kinetics (100% in 3 weeks), was internalized in murine and human cancer cells, and induced significantly higher toxic effects against a panel of tumor cell lines (2- to 40-fold lower IC50 values) compared to free DTX.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.033
GPT teacher head0.256
Teacher spread0.223 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations93
Published2011
Admission routes1
Has abstractyes

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