Polymer polymeric micelles

Keywords Sirolimus, cyclosporine, tacrolimus, mycophenolic add, drug-eluting stent, durable polymer, biodegradable polymer, bioresorbable polymer, polymeric micelle, nanoparticle... 

Figure C2.3.11 Key surfactant stmctures (not to scale) in emulsion polymerization micelles containing monomer and oligomer, growing polymer particle stabilized by surfactant and an emulsion droplet of monomer (reservoir) also coated with surfactant. Adapted from figure 4-1 in [67],...

Soap. A critical ingredient for emulsion polymerization is the soap (qv), which performs a number of key roles, including production of oil (monomer) in water emulsion, provision of the loci for polymerization (micelle), stabilization of the latex particle, and impartation of characteristics to the finished polymer. 

A number of examples have been studied in recent years, including liquid sulfur [1-3,8] and selenium [4], poly(o -methylstyrene) [5-7], polymer-like micelles [9,11], and protein filaments [12]. Besides their importance for applications, EP pose a number of basic questions concerning phase transformations, conformational and relaxational properties, dynamics, etc. which distinguish them from conventional dead polymers in which the reaction of polymerization has been terminated. EP motivate intensive research activity in this field at present. 

The overall objective of this chapter is to review the fundamental issues involved in the transport of macromolecules in hydrophilic media made of synthetic or naturally occurring uncharged polymers with nanometer-scale pore structure when an electric field is applied. The physical and chemical properties and structural features of hydrophilic polymeric materials will be considered first. Although the emphasis will be on classical polymeric gels, discussion of polymeric solutions and nonclassical gels made of, for example, un-cross-linked macromolecular units such as linear polymers and micelles will also be considered in light of recent interest in these materials for a number of applications... 

Oheme and co-workers investigated335 in an aqueous micellar system the asymmetric hydrogenation of a-amino acid precursors using optically active rhodium-phosphine complexes. Surfactants of different types significantly enhance both activity and enantioselectivity provided that the concentration of the surfactants is above the critical micelle concentration. The application of amphiphilized polymers and polymerized micelles as surfactants facilitates the phase separation after the reaction. Table 2 shows selected hydrogenation results with and without amphiphiles and with amphiphilized polymers for the reaction in Scheme 61.335... 

Fig. 30 Types of nanocarriers for drug delivery, (a) Polymeric nanoparticles polymeric nanoparticles in which drugs are conjugated to or encapsulated in polymers, (b) Polymeric micelles amphiphilic block copolymers that form nanosized core-shell structures in aqueous solution. The hydrophobic core region serves as a reservoir for hydrophobic drugs, whereas hydrophilic shell region stabilizes the hydrophobic core and renders the polymer water-soluble.

Synthetic polyisoprene, 9 559 Synthetic polymer architectures, 26 786 Synthetic polymeric micelles, 20 482 Synthetic polymers... 

We have shown that polymeric micelles constmcted of block copolymers of poly(ethylene oxide) (PEG) and poly(L-asparate) containing the anticancer dmg (adriamycin, ADR) selectively accumulate at solid tumor sites by a passive targeting mechanism. This is likely due to the hydrophilicity of the outer PEG chains and micellar size (<100 nm) that allow selective tissue interactions [17,18]. Polymeric micelle size ranges are tailored during polymer synthesis steps. Carefully selection of block polymer chemistry and block lengths can produce micelles that inhibit nonselective scavenging by the reticuloendothelial system (RES) and can be utilized as targetable dmg... 

Polymeric micelles, stars and dendrimers in solution consist of a number of polymer chains that form relatively compact aggregates that exhibit internal dynamics and overall diffusion. Whereas the association of polymer in a micelle is usually driven by physical interactions, the star and dendrimer architecture is generally achieved by chemical bonds. 

Polymeric micelles are mostly small (10-100 nm) in size and dmgs can be incorporated by chemical conjugation or physical entrapment. For efficient delivery activity, they shonld maintain their integrity for a sufficient amount of time after injection into the body. Most of the experience with polymeric micelles has been obtained in the field of passive targeting of anticancer drugs to tumours [33]. Attachment of antibodies or sugars, or introduction of a polymer sensitive to variation in temperature or pH has also been stndied [32]. 

Polymerization continues in stage II, and monomer continues to be supplied to the particles by the droplets in the aqueous phase. These droplets disappear when about 30% of the monomers has been converted to polymers. Polymerization continues in stage III after about 60% conversion, but all monomers must now be supplied to the macroradicals by a diffusion process in the micelles. 

One of the possible alternative to micelles are spherical dendrimers of diameter generally ranging between 5 and 10 nm. These are highly structured three-dimensional globular macromolecules composed of branched polymers covalently bonded to a central core [214]. Therefore, dendrimers are topologically similar to micelles, with the difference that the strnctnre of micelles is dynamic whereas that of dendrimers is static. Thus, unlike micelles, dendrimers are stable nnder a variety of experimental conditions. In addition, dendrimers have a defined nnmber of fnnctional end gronps that can be functionalized to prodnce psendostationary phases with different properties. Other psendostationary phases employed to address the limitations associated with the micellar phases mentioned above and to modnlate selectivity include water-soluble linear polymers, polymeric surfactants, and gemini snrfactant polymers. 

In addition to the micelle-type assemblies described above, there has been significant interest in developing conditions for forming vesicle-type assemblies from amphiphilic polymers. Polymeric vesicles are formed by bolamphiphilic block... 

Jeong JH, Park TG. Novel polymer-DNA hybrid polymeric micelles composed of hydrophobic poly(DL-lactic acid-co-glycolic acid) and hydrophiUc oligonucleotides. Bioconjugate Chem 2001 12 917-923. 

Description of the different mimetic systems will be the starting point of the presentation (Sect. 2). Preparation and characterization of monolayers (Langmuir films), Langmuir-Blodgett (LB) films, self-assembled (SA) mono-layers and multilayers, aqueous micelles, reversed micelles, microemulsions, surfactant vesicles, polymerized vesicles, polymeric vesicles, tubules, rods and related SA structures, bilayer lipid membranes (BLMs), cast multibilayers, polymers, polymeric membranes, and other systems will be delineated in sufficient detail to enable the neophyte to utilize these systems. Ample references will be provided to primary and secondary sources. 

When the macromonomer is an amphiphilic polymer, its polymerization in the polar media is unusually rapid as a result of its organization into micelles. Under such conditions, the unsaturated groups are concentrated in the micelle they mostly form the hydrophobic core of aggregates (micelles). During the polymerization, the non-polymerizing micelles and/or the monomer saturated continuous phase act as a monomer reservoir. 

Pharmaceutical research on polymeric micelles has mainly focused on two kinds of block copolymers, namely, AB block copolymers or diblock copolymers and ABA or BAB block copolymers known as triblock copolymers (Bader et al., 1984 Yokoyama et al., 1990,1991 Kwon and Okano, 1996, 1999 Kwon, 1998, 2003 Alakahov and Kabanov, 1998). The most common hydrophilic block (A) of the block copolymers is polyethylene oxide (PEO). This polymer is highly hydrated through hydrogen bonding and sterically stabilizes surfaces of the polymeric micelles in aqueous systems. 

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