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Brushed Block Copolymer Micelles with pH-Sensitive Pendant Groups for Controlled Drug Delivery

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ABSTRACT

Purpose

To investigate the effects of small aliphatic pendent groups conjugated through an acid-sensitive linker to the core of brushed block copolymer micelles on particle properties.

Methods

The brushed block copolymers were synthesized by conjugating five types of 2-alkanone (2-butanone, 2-hexanone, 2-octanone, 2-decanone, and 2-dodecanone) through an acid-labile hydrazone linker to poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers.

Results

Only block copolymers with 2-hexanone and 2-octanone (PEG-HEX and PEG-OCT) formed micelles with a clinically relevant size (< 50 nm in diameter), low critical micelle concentration (CMC, < 20 μM), and drug entrapment yields (approximately 5 wt.%). Both micelles degraded in aqueous solutions in a pH-dependent manner, while the degradation was accelerated in an acidic condition (pH 5.0) in comparison to pH 7.4. Despite these similar properties, PEG-OCT micelles controlled the entrapment and pH-dependent release of a hydrophobic drug most efficiently, without altering particle size, shape, and stability. The molecular weight of PEG (12 kDa vs 5 kDa) induced no change in pH-controlled drug release rates of PEG-OCT micelles.

Conclusion

Acid-labile small aliphatic pendant groups are useful to control the entrapment and release of a hydrophobic drug physically entrapped in the core of brushed block copolymer micelles.

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ACKNOWLEDGMENTS AND DISCLOSURES

This research is supported by the Kentucky Lung Cancer Research Program.

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Authors and Affiliations

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

    Hyun Jin Lee & Younsoo Bae

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  1. Hyun Jin Lee
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  2. Younsoo Bae
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Correspondence to Younsoo Bae.

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Lee, H.J., Bae, Y. Brushed Block Copolymer Micelles with pH-Sensitive Pendant Groups for Controlled Drug Delivery. Pharm Res 30, 2077–2086 (2013). https://doi.org/10.1007/s11095-013-1060-1

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  • DOI: https://doi.org/10.1007/s11095-013-1060-1

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