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Barbour, Nancy P.; Paborji, Mehdi; Alexander, Thomas C.; Coppola, William P.; Bogardus, Joseph B.

doi:10.1023/a:1016274825322

Cited by 13 publications

(4 citation statements)

References 9 publications

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“…The hydrazone moiety was selected for its high stability at physiological pH, and lability under strongly acidic and basic conditions as demonstrated by drug delivery agents in tumor targeting. [9][10][11] To our knowledge, such a click approach with 99m Tc has not yet been explored. Instead, the paradigm from the literature indicates that hydrazine precursors would be unavailable for hydrazone formation because they interact with 99m Tc metal centers.…”

mentioning

confidence: 99%

The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals

et al. 2011

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mentioning

confidence: 99%

The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals

et al. 2011

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“…Long term storage of polymer drug conjugates resulted in hydrolysis of the hydrazone bond during storage [similar to a previous study (32)] was identified by mathematical modeling of altered release kinetics after storage. This possible instability was explored and later confirmed experimentally.…”

Section: Introductionmentioning

confidence: 73%

“…The degradation mechanism was beyond the scope of this work, but the most likely possibility was hydrolysis during storage at −20°C due to the presence of trace amounts of water. Previously the hydrazone linkage in a Dox conjugate was shown to degrade after lyophilization during storage at 2 – 8°C (32). In that study, a water content of 2% in lyophilized samples resulted in 20% degradation of the hydrazone bond after 12 months.…”

Section: Discussionmentioning

confidence: 99%

Release, Partitioning, and Conjugation Stability of Doxorubicin in Polymer Micelles Determined by Mechanistic Modeling

et al. 2014

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Purpose To better understand the mechanistic parameters that govern drug release from polymer micelles with acid-labile linkers. Methods A mathematical model was developed to describe drug release from block copolymer micelles composed of a poly(ethylene glycol) shell and a poly(aspartate) core, modified with drug binding linkers for pH-controlled release [hydrazide (HYD), aminobenzoate-hydrazide (ABZ), or glycine-hydrazide (GLY)]. Doxorubicin (Dox) was conjugated to the block copolymers through acid-labile hydrazone bonds. The polymer drug conjugates were used to prepare three polymer micelles (HYD-M, ABZ-M, and GLY-M). Drug release studies were performed to identify the factors governing pH-sensitive release of Dox. The effect of prolonged storage of copolymer material on release kinetics was also observed. Results Biphasic drug release kinetics were observed for all three micelle formulations. The developed model was able to quantify observed release kinetics upon the inclusion of terms for unconjugated Dox and two populations of conjugated Dox. Micelle/water partitioning of Dox was also incorporated into the model and found significant in all micelles under neutral conditions but reduced under acidic conditions. The drug binding linker played a major role in drug release as the extent of Dox release at specific time intervals was greater at pH 5.0 than at pH 7.4 (HYD-M > ABZ-M > GLY-M). Mathematical modeling was also able correlate changes in release kinetics with the instability of the hydrazone conjugation of DOX during prolonged storage. Conclusion These results illustrate the potential utility of mechanistic modeling to better assess release characteristics intrinsic to a particular drug/nanoparticle system.

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“…Immunotoxins where the cytotoxic drug is conjugated by a peptide linker are also known. A widely investigated example is the BR96-DOX conjugate, where an average of 8 molecules of DOX are linked to chimeric mAB BR 96 through an acid-sensitive hydrazone linkage [179]. Promising immunotoxins currently in clinical trials include TransMID 107 (transferrin-CRM107), PRECISE (IL13-PEI-301-R03) [24].…”

Section: Immunotoxinsmentioning

confidence: 99%

Recent Trends in Targeted Anticancer Prodrug and Conjugate Design

Singh¹,

Palombo²,

Sinko³

2008

CMC

202

136

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Anticancer drugs are often nonselective antiproliferative agents (cytotoxins) that preferentially kill dividing cells by attacking their DNA at some level. The lack of selectivity results in significant toxicity to noncancerous proliferating cells. These toxicities along with drug resistance exhibited by the solid tumors are major therapy limiting factors that result into poor prognosis for patients. Prodrug and conjugate design involves the synthesis of inactive drug derivatives that are converted to an active form inside the body and preferably at the site of action. Classical prodrug and conjugate design have focused on the development of prodrugs that can overcome physicochemical (e.g., solubility, chemical instability) or biopharmaceutical problems (e.g., bioavailability, toxicity) associated with common anticancer drugs. The recent targeted prodrug and conjugate design, on the other hand, hinge on the selective delivery of anticancer agents to tumor tissues thereby avoiding their cytotoxic effects on noncancerous cells. Targeting strategies have attempted to take advantage of low extracellular pH, elevated enzymes in tumor tissues, the hypoxic environment inside the tumor core, and tumor-specific antigens expressed on tumor cell surfaces. The present review highlights recent trends in prodrug and conjugate rationale and design for cancer treatment. The various approaches that are currently being explored are critically analyzed and a comparative account of the advantages and disadvantages associated with each approach is presented.

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Untitled

Cited by 13 publications

References 9 publications

The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals

The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, 99mTc) radiopharmaceuticals

Release, Partitioning, and Conjugation Stability of Doxorubicin in Polymer Micelles Determined by Mechanistic Modeling

Recent Trends in Targeted Anticancer Prodrug and Conjugate Design

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