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. 2009 Apr 8;131(13):4830-8.
doi: 10.1021/ja809475a.

Multi-stimuli sensitive amphiphilic block copolymer assemblies

Akamol Klaikherd  1 , Chikkannagari Nagamani, S Thayumanavan
Affiliations

Multi-stimuli sensitive amphiphilic block copolymer assemblies

Akamol Klaikherd et al. J Am Chem Soc. .

Abstract

Stimuli-responsive polymers are arguably the most widely considered systems for a variety of applications in biomedical arena. We report here a novel triple stimuli sensitive block copolymer assembly that responds to changes in temperature, pH and redox potential. Our block copolymer design constitutes an acid-sensitive THP-protected HEMA as the hydrophobic part and a temperature-sensitive PNIPAM as the hydrophilic part with an intervening disulfide bond. The micellar properties and the release kinetics of the encapsulated guest molecule in response to one stimulus as well as combinations of stimuli have been evaluated. Responsiveness to combination of stimuli not only allows for fine-tuning the guest molecule release kinetics, but also provides the possibility of achieving location-specific delivery.

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Figures

Scheme 1
Scheme 1
Design of amphiphilic diblock copolymer: Schematic representation of amphiphilic block copolymer which can respond to three stimuli; pH, temperature and redox.
Scheme 2
Scheme 2
Synthesis of BCP from its homopolymers
Figure 1
Figure 1
Characterization of block copolymer (BCP) (a) the GPC profile showing the formation of block copolymer (BCP) (b) 1H NMR of BCP and its homopolymers.
Figure 2
Figure 2
Micellar assembly (a) Photograph shows an aqueous solution of BCP; (left) before adding Nile red, (right) after adding Nile red. (b) Plot of fluorescence intensity of Nile red vs. concentration of BCP. (c) Size of the micelle at 0.2 mg/mL determined by DLS experiment.
Figure 3
Figure 3
Acid sensitivity of BCP a) pH dependent release of Nile red from micellar assembly, b) Time dependent DLS profile of BCP solution in sodium acetate buffer of pH 4.0 (50mM), c) 1HNMR of BCP before and after treatment with sodium acetate buffer of pH 4.0 (50mM).
Figure 4
Figure 4
Temperature sensitivity of BCP a) photograph showing an aqueous solution of BCP; left-at room temperature, right-after heating to 40 °C, b) Turbidity experiment showing the change in HT voltage with temperature of BCP and PNIPAM.
Figure 5
Figure 5
Redox sensitivity of BCP a) GPC profile of BCP compared with the BCP solution treated with DTT and physical mixture of P1 and P3, b) turbidity of micellar solution upon treatment with DTT, c) % release of Nile red from micellar interior.
Figure 6
Figure 6
Dual stimuli responsive micelle a) Temperature-acid sensitive behavior, b) Temperature-redox sensitive behavior.
Figure 7
Figure 7
pH-redox responsive micelle (a) % release of Nile red from BCP solution treated with sodium acetate buffer of pH 5.0 (50mM) and Glutathione (1mg/mL, 3.2 mM) (b) Time dependent DLS profile of BCP solution in sodium acetate buffer of pH 5.0 (50mM) and Glutathione (1mg/mL, 3.2 mM)
Figure 8
Figure 8
Triple stimuli sensitive micelle.
See this image and copyright information in PMC

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