Polymeric micelle systems

As compared with other types of carrier systems, the polymeric micelle systems possess several beneLts (Yokoyama, 1992, 1994) including the wide applicability of polymeric micelle systems to drugs, through either chemical conjugation or physical entrapment and the small size of polymeric micelles. In the case of physical entrapment, utilizing hydrophobic interactions can be applied to many kinds of drugs (Kwon et al., 1994) because most drugs contain hydrophobic moiety(ies) in their chemical structures. 

The size of polymeric micelles, with an approximate diameter range of 20 to 60 nm, is smaller than achievable by liposomes and micro(nano)spheres. The smaller carrier systems are expected to show higher vascular permeability at target sites by a diffusion mechanism. Furthermore, the diameter range of the polymeric micelle systems is considered to be appropriate to evade renal excretion and nonspeciLc capture by the reticuloendothelial systems (RES). 

Block copolymer micelle formulations of doxorubicin and paclitaxel are both in Phase l/ll trials for the treatment of advanced cancers. Aliabadi and Lavasanifar (2006) recently compiled a review of the clinical status of polymeric micelle systems for anticancer agent delivery. 

Polymeric micelles were developed as a tumor-targeted delivery system for poorly water-soluble and toxic anticancer drugs. Preclinical studies have demonstrated reduced toxicity and enhanced accumulation of drugs in tumors with polymeric micelle systems. Issues such as sufficient in vivo stability and programmable drug release at the tumor sites need to be addressed in the future. 

Several methods for effective solubilization of drugs into polymer micelles have been developed (Fig. 2). The dialysis method (Fig. 2A) is most widely used for many polymeric micelle systems. The first step involves the dissolution of both polymer and drug in a water-miscible organic solvent such as acetonitrile, acetone, dimethylformamide, or ethanol. Then, the polymer-drug solution is dialyzed against water. As the organic... 

Huh, K.M. Lee, S.C. Lee, J. Cho, Y.W. Park, K. Hydro-tropic polymeric micelle systems for formulation of poorly water-soluble drugs. The 8th European Symposium on Controlled Drug Delivery 2004, 8, 19-21. 

In PEG-based polymeric micelle systems, the PEG shell contributes to the steric stabihty of the micelle by physically blocking the flocculation and prevents any non-specific interaction with blood components. The length and density of the PEG chain influence the circulation time and uptake by the RES, with longer chains prolonging the circulation time and decreasing the RES uptake [40]. Thus, encapsulation in the optimized polymeric micelles maybe a viable approach to prolonging the circulation time of therapeutic agents. 

Zhang C, Ding Y et al (2007) Polymeric micelle systems of hydroxycamptothecin based on amphiphilic N-alkyl-N-trimethyl chitosan derivatives. Colloids Surf B 55 192-199... 

Yokoyama and colleagues succeeded in getting an anticancer drug, ADR (=doxorubicin), with a polymeric micelle system,... 

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. 

Boston, Mas., 23rd-27th Aug. 1998, p.278-9. 012 POLYMERIC MICELLE SYSTEM FOR DRUG TARGETING... 

Release kinetics of taxol from OCL worm micelles was studied by dialysis method under sink condition . Figure 7 shows the percentage of taxol released from OCLl and OCL3 worm micelles versus time at 37 C, under pH 5 Hepes and pH 7 PBS physiological buffers respectively. After an initial burst release, typical for polymeric micelle systems (7), a much slower and sustained release... 

A large variety of drug delivery systems are described in the literature, such as liposomes (Torchilin, 2006), micro and nanoparticles (Kumar, 2000), polymeric micelles (Torchilin, 2006), nanocrystals (Muller et al., 2011), among others. Microparticles are usually classified as microcapsules or microspheres (Figure 8). Microspheres are matrix spherical microparticles where the drug may be located on the surface or dissolved into the matrix. Microcapsules are characterized as spherical particles more than Ipm containing a core substance (aqueous or lipid), normally lipid, and are used to deliver poor soluble molecules... 

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... 

The copolymer-based systems possessing the core-shell structure in solutions are known and studied rather well (see, e.g., [14-16]). These copolymers in aqueous media tend to form polymeric micelles, which are often considered as promising drug delivery nano-vehicles [ 17,18], i.e., these macromolecular systems are not only of scientific, but also of considerable applied significance. Among such systems there are interesting examples, whose properties are very similar to the properties that should be inherent in the protein-like copolymers. All of these macromolecules possess the primary structure of... 

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... 

In many cases in drug development, the solubility of some leads is extremely low. Fast dissolution rate of many drug delivery systems, for example, particle size reduction, may not be translated into good Gl absorption. The oral absorption of these molecules is usually limited by solubility (VWIImann et al., 2004). In the case of solubility limited absorption, creating supersaturation in the Gl Luids for this type of insoluble drugs is very critical as supersaturation may provide great improvement of oral absorption (Tanno et al., 2004 Shanker, 2005). The techniques to create the so-called supersaturation in the Gl Luids may include microemulsions, emulsions, liposomes, complexations, polymeric micelles, and conventional micelles, which can be found in some chapters in the book. 

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