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Comparison of Dialysis- and Solvatofluorochromism-Based Methods to Determine Drug Release Rates from Polymer Nanoassemblies

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Abstract

Purpose

To compare traditional dialysis- and novel solvatofluorochromism (SFC)-based methods for accurate determination of drug release profiles for nanoparticle drug carriers.

Methods

Polymer nanoassemblies (PNAs) varying in drug release patterns were prepared using poly(ethylene glycol), poly(ethylenimine), hydrophobic excipients (palmitate and deoxycholate), and model hydrophobic anticancer drugs with clinical relevance (carfilzomib and docetaxel). Nile blue (NB) was used as a model SFC dye quenching fluorescence in water yet emitting strong fluorescence in the presence of hydrophobic drugs within PNAs. Drug release kinetics were measured by dialysis- and SFC-based methods, and analyzed by mathematical modeling of free drug, spiked drug, and encapsulated drug release.

Results

The dialysis method overestimated drug remaining in PNAs because it included released drug in measurements, whereas the SFC method successfully distinguished drugs entrapped in PNAs from released in solution and thus provided more accurate drug release patterns. However, mathematical modeling revealed that the dialysis method would be less influenced than the SFC method by hydrophobic excipients modulating drug diffusion within PNAs.

Conclusions

In comparison to the dialysis-based method, the SFC-based method would allow for real-time spectroscopic determination of drug release from PNAs and potentially other nanoparticle drug carriers with improved convenience and accuracy.

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Abbreviations

2P:

PEG-PEI

2PN:

PEG-PEI-NB

3P:

PEG-PEI-PAL

3PN:

PEG-PEI-PAL-NB

CFZ:

Carfilzomib

DOC:

Docetaxel

DOCA:

Deoxycholic acid

NB:

Nile blue

PAL:

Palmitic acid

PEG:

Poly(ethylene glycol)

PEI:

Poly(ethylenimine)

PNAs:

Polymer nanoassemblies

SFC:

Solvatofluorochromism

TNAs:

Tethered polymer nanoassemblies

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ACKNOWLEDGMENTS AND DISCLOSURES

DR acknowledges financial support from the University of Kentucky College of Pharmacy Graduate School Allocated Year (GSAY) Fellowship.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky, 40536-0596, USA

    Derek Reichel & Younsoo Bae

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  1. Derek Reichel
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  2. Younsoo Bae
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Correspondence to Younsoo Bae.

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Reichel, D., Bae, Y. Comparison of Dialysis- and Solvatofluorochromism-Based Methods to Determine Drug Release Rates from Polymer Nanoassemblies. Pharm Res 34, 394–407 (2017). https://doi.org/10.1007/s11095-016-2070-6

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  • DOI: https://doi.org/10.1007/s11095-016-2070-6

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