Block copolymer micelles in aqueous solution

R. Nagarajan, Solubilization of Hydrophobic Substances by Block Copolymer Micelles in Aqueous Solution, in Solvents and Self-Organization of Polymers (eds. S. E. Webber, P. Munk and Z. Tuzar), Kluwer Publishers, Amsterdam, 1988. 

Fluorescence Spectroscopy Studies of Amphiphilic Block Copolymer Micelles in Aqueous Solutions... 

Abstract We discuss applications of selected fluorescence spectroscopy techniques for the studies of block copolymer micelles in aqueous solution, focusing on solvent relaxation measurements using polarity-sensitive fluorescent probes, oti fluorescence quenching studies, and on using fluorescent pH indicators for studies... 

Since synthetic copolymers seldom exhibit intrinsic fluorescence, either covalently bound fluorescent labels or non-covalently bound fluorescent probes are necessary for the vast majority of fluorescence studies of block copolymer micelles. The former are mostly attached during the synthesis of the copolymer [18]. This could be done conveniently by using a fluorescent initiator and/or fluorescent terminating agent. In such cases, the labels are located at the ends of the blocks or in between of them. Fluorescent probes can be used for studies of amphiphilic block copolymer micelles in aqueous solutions where strong hydrophobic effect allows for binding of the probe either in the micellar core (hydrophobic probes) [19] or in the iruier part of the shell close to the core/shell interface (amphiphilic probes) [20]. The latter, developed mainly for membrane studies, are derivatives of... 

While there are many papers in the literature on the solvent relaxation in solutions of proteins, surfactant micelles, and phospholipid vesicles studied by time-resolved emission spectroscopy [25-27], similar studies focused on block copolymer micelles are scarce. In most cases, amphiphilic fluorescent probes localized in the inner part of the shells of amphiphilic block copolymer micelles in aqueous solutions were used for the studies. The studies reveal the heterogeneity of the binding sites of the probe that manifest itself by multiple-exponential fluorescence decays. In the case of block copolymer micelles, interpretation of the relaxation behavior can be complicated by redistribution of the probe molecules in the micelles during its excited-state lifetime of the probe [28]. The redistribution occurs as a result of the increased polarity of the excited probe as compared with its ground electronic state. 

Waton, G., Michels, B., Zana, R. Dynamics of block copolymer micelles in aqueous solution. Macromolecules 2001, 34(4), 907-910. 

Desai PR, Jain NJ, Sharma RK, Bahadur P (2001) Effect of additives on the micellization of PEO/PPO/PEO block copolymer F127 in aqueous solution. Colloid Surf A 178 57-69... 

For some applications, it is desirable to lock the micellar structure by cross-Hnking one of the micellar compartments, as discussed previously in Sect. 2.6. Cross-Hnked core-shell-corona micelles have been prepared and investigated by several groups as illustrated by the work of Wooley and Ma [278], who reported the cross-linking of PS-PMA-PAA micelles in aqueous solution by amidation of the PAA shell. Very recently, Wooley et al. prepared toroidal block copolymer micelles from similar PS-PMA-PAA copolymers dissolved in a mixture of water, THF, and 2,2-(ethylenedioxy)diethylamine [279]. Under optimized conditions, the toroidal phase was the predominant structure of the amphiphilic triblock copolymer (Fig. 19). The collapse of the negatively charged cylindrical micelles into toroids was found to be driven by the divalent 2,2-(ethylenedioxy)diethylamine cation. 

Torchilin et al. synthesized an iodine-containing amphiphilic block-copolymer consisting of iodine-substituted poly-L-lysine which is able to form micelles in aqueous solution [37]. The two components of the block-copolymer were methoxy-poly(ethylene glycol) propionic acid (MPEG-PA) with a molecular weight of 12 kDa and poly[ ,M-(2,3,5-triiodobenzoyl)]-L-lysine. The particle size of the micelles was approx. 80 nm, and the iodine concentration was 20 mg mL . Biodistribution studies in rats showed significant and prolonged enhancement of the aorta, the liver and spleen. 

The ethylene oxide block is hydrophilic, whereas the propylene oxide block is (relatively) hydrophobic. The copolymer forms micelles in aqueous solutions with the hydrophilic portions pointing outward, interacting with the water, while the hydrophobic portions form the inner core, shielded from the water by the ethylene oxide-derived block. A micelle is also formed in organic liquids, but here the hydrophobic propylene oxide block faces outward, whereas the ethylene oxide bloek acts as the inner eore. 

Sha et al. applied the commercially available dual initiator ATRP-4 for the chemoenzymatic synthesis of block copolymers. In a first series of publications, the group reported the successful synthesis of a block copolymer comprising PCL and polystyrene (PS) blocks [31, 32]. This concept was then further applied for the chemoenzymatic synthesis of amphiphilic block copolymers by macroinitiation of glycidyl methacrylate (GMA) from the ATRP functional PCL [33]. This procedure yielded well-defined block copolymers, which formed micelles in aqueous solution. Sha et al. were also the first to apply the dual enzyme/ATRP initiator concept to an enzymatic polycondensation of 10-hydroxydecanoic acid [34]. This concept was then extended to the ATRP of GMA and the formation of vesicles from the corresponding block copolymer [35]. 

Much recent work on micellization in block copolymers has been focussed on this industrially important type of polymer. We therefore describe experiments on micellization in aqueous solutions of poly(oxyalkylene) diblocks and triblocks in some detail. This serves to illustrate many of the important features of micellization of block copolymers, also observed in other systems such as the styrenic block copolymers covered in the following section. 

The PEO-rich PSt-h-PEO block copolymers form spherical micelles in aqueous solutions [63]. The DLS measurements indicate the presence of a bimodal size distribution - two very narrowly distributed species. The smaller more mobile species had Rh corresponding to the star model of block copolymer micelles. However, 99% or more of the block copolymer is present as simple micelles. 

These block-copolymers form micelles in aqueous solution with spherical core/shell structures and diameters around 20-40 nm (Figure 5.9). The hydrophobic core of these micelles can be loaded with a hydrophobic drug such as doxorubicin. After intravenous administration the micelles tend to accumulate at tumor sites and release the entrapped drug there. Some of the characteristics of these micellar systems are listed in Table 5.5. 

Bioerodible poly(ortho ester) copolymers containing hydrophilic and hydrophobic blocks have been prepared from di(ketene acetals) and oligomeric diols. These materials form micelles in aqueous solution making them useful as hydrophobic encapsulation agents or as bioerodible matrices for the sustained release of medicaments. 

Block copolymers of 23b and alkyl methacrylates [158] and diblock copolymers of 23b with 2-(diethylamino)ethyl methacrylate (23b-DEAEM), 2-(diisopropylamino)ethyl methacrylate (23b-DIPAEM), or 2-(N-morphoHno) ethyl methacrylate (23b-MEMA) exhibited reversible pH-, salt-, and temperature-induced micellization in aqueous solution under various conditions. The micelle diameters were 10-46 nm [238]. The micelles of these hydropho-bically modified polybetaines consist of coronas from 23b and cores from polyDEAEM, polyDIPAEM, or polyMEMA. In aqueous solution, the 23b-MEMA diblock copolymers form micelles with cores of polyMEMA above an upper critical micelle temperature of about 50 °C, and reversibly betainized-DMAEM core micelles below a lower critical micelle temperature of approximately 20 °C [239]. 

Recently, novel micellar systems based on block copolymers have been developed for drug solubilization and delivery (Houlton, 2003). One example of such a system is poly-ethylene glycol-poly-aspartic acid block copolymer, which spontaneously forms into colloidal particles (micelles) in aqueous solution. In this type of micelle, the drug molecule will experience an environment characterized by the physicochemical properties of the polymer (see Section 16.2.2.3). 

Methyl methacrylate (MMA) and sodium styrene sulfonate (SSNa) are water-soluble. These polymers behave like a low MW surfactant as they form micelles in aqueous solution in which the hydrophobic part is directed towards the centre and the hydrophilic part is situated on the periphery of the micelle. Owing to such features, amphiphilic block copolymers have wide-ranging applications in drugs, pharmaceuticals, coatings, cosmetics and paints. They also exhibit very high antibacterial activities. Oikonomou and co-workers used ATRP to prepare amphiphilic block copolymers, consisting of polymethyl methacrylate (PMMA) and poly (sodium styrene sulfonate) (PSSNa) blocks [18]. The synthesis methods are described below. 

We have shown that a combination of four simple building blocks (i.e. monomers) and exclusively non-covalent interaction forces, achieved via the co-assembly of fully water-soluble double hydrophilic block copolymers, results in mixed micelles in aqueous solutions. The chemically unlike polymer chains in the micellar corona may give rise to various coronal microstructures, ranging from mixed to segregated, in either the radial or lateral direction, or in both. Hence, co-assembly of charged block copolymers can result in the spontaneous formation of reversible Janus micelles. 

The kinetics of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers have been intensively studied by T-jump experiments with light scattering detection [115, 126-130]. PEO-PPO-PEO triblock copolymers form micelles in aqueous solution, with PPO as the core forming hydrophobic block. Above the critical micelle concentration (cmc) and critical micelle temperature there exists a transition region of AT 10-15 C where... 

Pluronics, also known as poloxamers, are a class of synthetic block copolymers which consist of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO), arranged in an A-B-A triblock structure, thus giving PEO-PPO-PEO (Fig. 11.7) (Batrakova and Kabanov 2008). They can be found either as liquids, pastes or solids (Ruel-Gariepy and Leroux 2004). Due to their amphiphilic characteristics (presence of hydrophobic and hydrophilic components), pluronics possess surfactant properties which allow them to interact with hydrophobic surfaces and biological membranes (Batrakova and Kabanov 2008). Being amphiphilic also results in the ability of the individual block copolymers, known as unimers, to combine and form micelles in aqueous solutions. When the concentration of the block copolymers is below that of the critical micelle concentration (CMC), the unimers remain as molecular solutions in water. However, as the block copolymer concentration is increased above the CMC, the unimers will self-assemble and form micelles, which can take on spherical, rod-shaped or lamellar geometries. Their shapes depend on the length and concentration of the block copolymers (i.e. EO and PO), and the temperature (Kabanov et al. 2002). Micelles usually have a hydrophobie eore, in this case the PO chains, and a hydrophilic shell, the EO ehains. 

In these studies we have used solution NMR to study structure formation and the intermolecular interactions between the polymer and the matrix during the cure that affect the miscibility. The triblock copolymers form micelles in aqueous solution with the propylene oxide block at the center and the ethylene oxide block at the exterior (6), and micelle formation can be monitored via the proton linewidths. The NMR studies show that the triblock copolymers do not form micelles in the butanol solutions used for solution casting films of the low-k dielectrics, or in neat mixtures of the triblock copolymers with the methyl silsesquioxane. The methyl silsesquioxane starting material contains a... 

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