pH-Sensitive Micelles Based on Double-Hydrophilic Poly(methylacrylic acid)-Poly(ethylene glycol)-Poly(methylacrylic acid) Triblock Copolymer
© to the authors 2009
Received: 30 November 2008
Accepted: 2 January 2009
Published: 21 January 2009
pH-sensitive micelles with hydrophilic core and hydrophilic corona were fabricated by self-assembling of triblock copolymer of poly(methylacrylic acid)-poly(ethylene glycol)-poly(methylacrylic acid) at lower solution pH. Transmission electron microscopy and laser light scattering studies showed micelles were in nano-scale with narrow size distribution. Solution pH value and the micelles concentration strongly influenced the hydrodynamic radius of the spherical micelles (48–310 nm). A possible mechanism for the formation of micelles was proposed. The obtained polymeric micelle should be useful for biomedical materials such as carrier of hydrophilic drug.
KeywordsSelf-assembly Micelles Double-hydrophilic Triblock copolymers
The self-assembly behavior of double-hydrophilic block copolymers under the influence of a given external stimulus, such as a change in pH, temperature, or ionic strength, has attracted considerable interests due to their potential application in areas such as biomimetic chemistry, molecular switch, and controlled drug delivery [1–4]. Many systems, such as poly(ethylene glycol)-block-poly(N-isopropylacrylamide) , poly(styrenesulfonic acid)-block-poly(methacrylic acid) , and poly(ethylene glycol)-block-poly(methacrylic acid) , have been investigated.
PMAA is one of the most commonly used hydrophilic polymers that possess several specific properties such as bioactive, pH, and ionic strength responsive properties. A number of polymeric micelles formed from PMAA-based amphiphilic diblock copolymers have been investigated for various applications [8, 9]. PEG is a noncharged, hydrophilic, and nonimmunogenic polymer that has found wide chemical, biomedical, and industrial applications [10, 11]. Complexation of PMAA with PEG has been extensively studied . Also, the micellization of PEG-b-PMAA diblock copolymers with linear structure, as well as with branched or graft architecture has recently been studied . However, there is no report on the self-assembly behavior of double-hydrophilic triblock copolymer of PEG and PMAA (PMAA-b-PEG-b-PMAA). Actually, triblock copolymer display very rich phase behavior and morphologies in solution, because of their special compositions and properties [13, 14]. Therefore, it is very interesting to have insight into the self-assembly behavior of this novel double-hydrophilic triblock copolymer PMAA-b-PEG-b-PMAA in aqueous solutions.
Based on the fact that the fabrication as well as the average size and size distribution of PMAA-b-PEG-b-PMAA micelles were strongly dependent on the pH value, a possible mechanism for the formation of PMAA-b-PEG-b-PMAA micelles at lower pH value was proposed and shown in Scheme 1. It is well-known that nonionized PMAA is water-soluble and has an hypercoiled conformation as result of the intramolecular hydrogen bonding of the MAA units when the solution pH was less than 6 . Therefore, above pH 6, PMAA-b-PEG-b-PMAA chains were in extended chain conformation due to the electrostatic repulsion between the PMAA segments . Decreasing the solution pH down to 6 caused the conformation change of PMAA segments from extended chain to hypercoil. This change of conformation resulted in the aggregation of PMAA chain segments into micellar core. Simultaneously, the middle block PEO self-assembled into micellar corona due to the back-folding and looping of PEO chain [13, 16]; therefore, the generation of micelles with water-soluble PMAA core and hydrophilic PEO loop chain corona was realized. The reason why minimum Rh and the narrowest size distribution occurred at pH 2.6 was not clear at this moment. Possibly, 2.6 was a critical pH value, and PMAA chains would more tightly aggregate at this value, resulting in firmly fixed micelles, whereas a further decrease below 2.6 caused much more aggregation of PMAA segments, leading to unstable micelles and even precipitation of the polymers.
The National Natural Science Foundation of China (NSFC50673038) is acknowledged for supporting this research.
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