Dataset Information

Colloidal Drug Aggregate Stability in High Serum Conditions and Pharmacokinetic Consequence.

ABSTRACT: Colloidal drug aggregates have been a nuisance in drug screening, yet, because they inherently comprise drug-rich particles, they may be useful in vivo if issues of stability can be addressed. As the first step toward answering this question, we optimized colloidal drug aggregate formulations using a fluorescence-based assay to study fulvestrant colloidal formation and stability in high (90%) serum conditions in vitro. We show, for the first time, that the critical aggregation concentration of fulvestrant depends on media composition and increases with serum concentration. Excipients, such as polysorbate 80, stabilize fulvestrant colloids in 90% serum in vitro for over 48 h. Using fulvestrant and an investigational pro-drug, pentyloxycarbonyl-( p-aminobenzyl) doxazolidinylcarbamate (PPD), as proof-of-concept colloidal formulations, we demonstrate that the in vivo plasma half-life for stabilized colloids is greater than their respective monomeric forms. These studies demonstrate the potential of turning the nuisance of colloidal drug aggregation into an opportunity for drug-rich formulations.

SUBMITTER: Ganesh AN

PROVIDER: S-EPMC6474797 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Colloidal Drug Aggregate Stability in High Serum Conditions and Pharmacokinetic Consequence.

Ganesh Ahil N AN Aman Ahmed A Logie Jennifer J Barthel Ben L BL Cogan Peter P Al-Awar Rima R Koch Tad H TH Shoichet Brian K BK Shoichet Molly S MS

ACS chemical biology 20190312 4

Colloidal drug aggregates have been a nuisance in drug screening, yet, because they inherently comprise drug-rich particles, they may be useful in vivo if issues of stability can be addressed. As the first step toward answering this question, we optimized colloidal drug aggregate formulations using a fluorescence-based assay to study fulvestrant colloidal formation and stability in high (90%) serum conditions in vitro. We show, for the first time, that the critical aggregation concentration of f ...[more]

PMID: 30840432

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Dataset Information

Colloidal Drug Aggregate Stability in High Serum Conditions and Pharmacokinetic Consequence.

Publications

Colloidal Drug Aggregate Stability in High Serum Conditions and Pharmacokinetic Consequence.

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