Comparison of Dialysis- and Solvatofluorochromism-Based Methods to Determine Drug Release Rates from Polymer Nanoassemblies
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To compare traditional dialysis- and novel solvatofluorochromism (SFC)-based methods for accurate determination of drug release profiles for nanoparticle drug carriers.
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.
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.
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.
KEY WORDScontrolled drug release drug release kinetics mathematical modeling nanoparticles solvatofluorochromism
Tethered polymer nanoassemblies
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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