Solubilized systems block copolymer micelles

Two models for micelle structure were identiLed in their studies (Xing and Mattice, 1998). In analogy with the structural models for systems involving low molecular weight surfactants, two kinds of aggregates of spherical shape can be pictured, depending on how the solubilizates are located inside the block copolymer micelles. Solubilization takes places in two steps in the Xing and Mattice s simulations (1998). 

The existence of nanostructures in polymeric systems assumes the presence of interfaces, so if these systems are solubilized in any solvent without loss of nanostructure (interfaces), they are not genuinely homogeneous, but rather nanoheterogeneous. In this case, interfaces are formed within a nanometer size volume, while these systems are colloidally soluble. Examples of such systems are various kinds of block copolymer micelles, microgels, and polymer colloids. 

The water solubiUty of PLA-PEG and PLGA-PEG copolymers depends on the molecular weight of the hydrophobic (PLGA-PEG) and hydrophilic (PEG) blocks. Water soluble PLA-PEG copolymers with relatively low molecular weight PLA blocks self-disperse in water to form block copolymer micelles. For example, water soluble PLA-PEG 2 5 (M of PLA 2000 Da and M of PEG is 5000 Dalton) form spherical micelles 25 run in diameter. These micelles solubilize model and anticancer drugs by micellar incorporation. However, in vivo, the systemic lifetimes produced were relatively short and the clearance rate was signihcantly faster when the micelles are administered at low concentration. This suggests micellar dissociation at concentrations below the cmc. 

These are stable micelles that are formed with polymeric surfactants. Amphiphilic block copolymers such as the pluronics (polyoxyethylene-polyoxypropylene block copolymers) are able to self-assemble into polymeric micelles and hydrophobic drugs may be solubilized within the core of the micelle or, alternatively, conjugated to the micelle-forming polymer. Although micelles are rather dynamic systems that continuously exchange units between the micelle structure and the free units in solution, those composed of polyoxyethylene - poly(aspartic acid) have been found sufficiently... 

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). 

For example, McCormick and coworkers [173] have dispersed pyrene in block copolymers of AMPS and 3-(acrylamido)-3-methylbutanoate (AMBA). The pH response of the system was investigated by using the sensitivity of the fluorescence spectrum of the probe to the polarity of the medium. Figure 2.12a shows an example of the spectra at two pH extremes the decrease in the intensity of band 1 from pH 9.0 to 1.0 is indicative of pyrene, which resides in a more hydrophobic environment and is consistent with the formation of micelles under acidic conditions. Figure 2.12b shows a plot of the resultant /1 to /3 ratio across the pH range. A dramatic decrease in the ratio is observed between pH 5.0 and 6.0. This supports NMR data, which indicates that dehydration of the PAMBA block occurs at pH 5.5, which serves to create near monodisperse micelles, which can solubilize low molar mass material. 

Polymeric micelle systems (PMS) are made by the self-assembly of amphiphilic block copolymers in an aqueous enviromnent. The important features of PMS are drug solubilization, controlled drug release, and drug targeting [26]. This chapter focuses and discusses the current scenario of natural biodegradable polymeric-based nanoblends for protein and gene delivery with a special emphasis on the pharmaceutical and biomedical approaches. 

After bioerosion of the poly(malonate) sequence the block copolymer will be formed by two water-soluble sequences which in contrast to the starting PEO-PMM 212 copolymer has no longer a tendency to form micelles. Solubilization of drugs in this type of bioerod-ible micelles appeared to be very promising as drug carrier and controlled delivery systems because their toxicity is quite reduced with respect to poly(cyanoacrylates). 

Apart from micelles, surfactants, block copolymers and polar lipids self-assemble to a wide range of liquid crystalline phases and microemulsions [Ij. These systems offer opportunities for increased solubilization of hydrophobic drugs. Similarly, due to their water compartments, some liquid crystalline phases (e.g. cubic) are also interesting delivery systems for proteins, peptides and other biomolecular drugs. Depending on its physicochemical properties, a drug incorporated in such self-assembly systems may localize preferentially in the oil or water compartment(s), or at the interface between these, thereby affecting the structure and stability of the self-assembled system. 

The book first discusses. self-assembling processes taking place in aqueous surfactant solutions and the dynamic character of surfactant self-assemblies. The next chapter reviews methods that permit the. study of the dynamics of self-assemblies. The dynamics of micelles of surfactants and block copolymers,. solubilized systems, microemulsions, vesicles, and lyotropic liquid crystals/mesophases are reviewed. successively. The authors point out the similarities and differences in the behavior of the.se different self-as.semblies. Much emphasis is put on the processes of surfactant exchange and of micelle formation/breakdown that determine the surfactant residence time in micelles, and the micelle lifetime. The la.st three chapters cover topics for which the dynamics of. surfactant self-assemblies can be important for a better understanding of observed behaviors dynamics of surfactant adsorption on surfaces, rheology of viscoelastic surfactant solutions, and kinetics of chemical reactions performed in surfactant self-assemblies used as microreactors. 

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